Peter Ward

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. pmc Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response
    Michael A Flierl
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
    PLoS ONE 4:e4414. 2009
  2. pmc Cross-talk between TLR4 and FcgammaReceptorIII (CD16) pathways
    Daniel Rittirsch
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS Pathog 5:e1000464. 2009
  3. pmc An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
    Andreas D Niederbichler
    Department of Surgery, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Exp Med 203:53-61. 2006
  4. pmc The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis
    Michael A Flierl
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 3:e2560. 2008
  5. pmc Regulatory effects of C5a on IL-17A, IL-17F, and IL-23
    Jamison J Grailer
    Department of Pathology, University of Michigan Medical School Ann Arbor, MI, USA
    Front Immunol 3:387. 2012
  6. pmc Manipulation of the complement system for benefit in sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, P O Box 5602, Ann Arbor, MI 48109 5602, USA
    Crit Care Res Pract 2012:427607. 2012
  7. pmc Modulation of inflammation by interleukin-27
    Markus Bosmann
    1 University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    J Leukoc Biol 94:1159-65. 2013
  8. pmc Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury
    Markus Bosmann
    1Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, Michigan 48109 5602
    FASEB J 27:5010-21. 2013
  9. doi request reprint The bipolar role of miR-466l in inflammation
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 5602, USA Electronic address
    Immunity 39:801-2. 2013
  10. pmc Opportunities and challenges of disease biomarkers: a new section in the Journal of Translational Medicine
    Xiangdong Wang
    Department of Respiratory Medicine, Biomedical Research Center, Zhongshan Hospital Qing Pu Branch, Fudan University, Shanghai, China
    J Transl Med 10:240. 2012

Research Grants

  1. Regulation of Lung Inflammation by Catecholamines and Adrenergic Receptors
    Peter A Ward; Fiscal Year: 2010
  2. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2005
  3. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2005
  4. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2002
  5. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2003
  6. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2006
  7. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2007
  8. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2007
  9. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2009
  10. Protective Effects of Anti-C5a in Sepsis
    Peter A Ward; Fiscal Year: 2010

Collaborators

Detail Information

Publications92

  1. pmc Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response
    Michael A Flierl
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
    PLoS ONE 4:e4414. 2009
    ....
  2. pmc Cross-talk between TLR4 and FcgammaReceptorIII (CD16) pathways
    Daniel Rittirsch
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS Pathog 5:e1000464. 2009
    ..In conclusion, our findings suggest that TLR4 and FcgammaRIII pathways are structurally and functionally connected at the receptor level and that TLR4 is indispensable for FcgammaRIII signaling via FcRgamma-subunit activation...
  3. pmc An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
    Andreas D Niederbichler
    Department of Surgery, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Exp Med 203:53-61. 2006
    ..These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a-C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance...
  4. pmc The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis
    Michael A Flierl
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 3:e2560. 2008
    ..Since blockade of both C5a receptors virtually abolished adrenomedullary apoptosis in vivo, C5aR and C5L2 become promising targets with implications on future complement-blocking strategies in the clinical setting of sepsis...
  5. pmc Regulatory effects of C5a on IL-17A, IL-17F, and IL-23
    Jamison J Grailer
    Department of Pathology, University of Michigan Medical School Ann Arbor, MI, USA
    Front Immunol 3:387. 2012
    ..The contributions of C5a interaction with its receptors in the production of IL-17/IL-23 and promotion of IL-17-dependent immune responses are reviewed...
  6. pmc Manipulation of the complement system for benefit in sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, P O Box 5602, Ann Arbor, MI 48109 5602, USA
    Crit Care Res Pract 2012:427607. 2012
    ..Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented...
  7. pmc Modulation of inflammation by interleukin-27
    Markus Bosmann
    1 University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    J Leukoc Biol 94:1159-65. 2013
    ....
  8. pmc Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury
    Markus Bosmann
    1Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, Michigan 48109 5602
    FASEB J 27:5010-21. 2013
    ..High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones...
  9. doi request reprint The bipolar role of miR-466l in inflammation
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 5602, USA Electronic address
    Immunity 39:801-2. 2013
    ..In this issue of Immunity, Li et al. (2013) describe bipolar roles for miR-466l in the promotion of inflammation and the induction of SPMs. ..
  10. pmc Opportunities and challenges of disease biomarkers: a new section in the Journal of Translational Medicine
    Xiangdong Wang
    Department of Respiratory Medicine, Biomedical Research Center, Zhongshan Hospital Qing Pu Branch, Fudan University, Shanghai, China
    J Transl Med 10:240. 2012
    ..Disease biomarkers are also important for determining drug effects, target specificities and binding, dynamic metabolism and pharmacological kinetics, or toxicity profiles...
  11. pmc Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis
    Michael A Flierl
    Department of Orthopaedics, School of Medicine, University of Colorado, Denver Health Medical Center, Denver, CO, 80204, USA
    Ann Intensive Care 1:53. 2011
    ..abstract:..
  12. pmc Therapeutic potential of targeting IL-17 and IL-23 in sepsis
    Markus Bosmann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
    Clin Transl Med 1:4. 2012
    ..Currently, it is not clear whether such findings can be translated to human sepsis. This review highlights the current knowledge on the biology of IL-17 isoforms and IL-23 as well as potential applications to clinical medicine...
  13. pmc New approaches to the study of sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
    EMBO Mol Med 4:1234-43. 2012
    ..The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved...
  14. pmc Anti-inflammatory effects of β2 adrenergic receptor agonists in experimental acute lung injury
    Markus Bosmann
    The University of Michigan Medical School, Department of Pathology, 1301 Catherine Rd Box 5602, Ann Arbor, MI 48109 5602, USA
    FASEB J 26:2137-44. 2012
    ..While β(2)AR agonists suppress JNK activation, the extent to which this can explain the blunted lung inflammatory responses in the ALI models remains to be determined...
  15. pmc Evidence for anti-inflammatory effects of C5a on the innate IL-17A/IL-23 axis
    Markus Bosmann
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    FASEB J 26:1640-51. 2012
    ..These data identify previously unknown mechanisms by which the anaphylatoxin C5a limits acute inflammation and antagonizes the IL-17A/IL-23 axis...
  16. pmc Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, Berlin, Germany
    J Neuroinflammation 4:13. 2007
    ..This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice...
  17. pmc Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, 12200 Berlin, Germany
    BMC Neurosci 7:55. 2006
    ....
  18. ncbi request reprint Evaluation of endotoxin models for the study of sepsis
    Daniel G Remick
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109 0602, USA
    Shock 24:7-11. 2005
    ..Compounds that have been shown to be effective at reducing mortality in endotoxin models should be re-evaluated in more clinically relevant models of sepsis...
  19. ncbi request reprint The dark side of C5a in sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109, USA
    Nat Rev Immunol 4:133-42. 2004
    ..This review describes our present understanding of how and why sepsis is a life-threatening condition and how it might be more effectively treated...
  20. pmc Sepsis, apoptosis and complement
    P A Ward
    The University of Michigan Medical School, Department of Pathology, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    Biochem Pharmacol 76:1383-8. 2008
    ....
  21. ncbi request reprint Role of the complement in experimental sepsis
    Peter A Ward
    University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109 0602, USA
    J Leukoc Biol 83:467-70. 2008
    ..In humans with septic shock, there is evidence of complement activation products in plasma along with loss of C5aRs on blood PMNs. These data suggest that in septic humans, interception of C5a or C5aR might be clinically efficacious...
  22. doi request reprint The first fifty years in research
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 5602, USA
    Annu Rev Pathol 4:1-18. 2009
    ..Rather, I have cited what I think are my most important publications, which identify many of these scientific colleagues. I am now engaged nearly full-time in research and look forward to the next period of research progress...
  23. ncbi request reprint Anti-complement strategies in experimental sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Scand J Infect Dis 35:601-3. 2003
    ..Studies are underway in humans with sepsis to determine whether similar mechanisms are in play...
  24. pmc Role of C5 activation products in sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
    ScientificWorldJournal 10:2395-402. 2010
    ..Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception...
  25. pmc Functions of C5a receptors
    Peter A Ward
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, 48109 0602, USA
    J Mol Med (Berl) 87:375-8. 2009
    ..Better definition of C5L2 is needed if its in vivo blockade, along with C5aR, is to be considered in complement-dependent inflammatory diseases...
  26. ncbi request reprint Endogenous regulation of the acute inflammatory response
    Peter A Ward
    Department of Pathology, University of Michigan, Ann Arbor 48109, USA
    Mol Cell Biochem 234:225-8. 2002
    ..These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the inflammatory response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines...
  27. ncbi request reprint Acute lung injury: how the lung inflammatory response works
    P A Ward
    Dept of Pathology, University of Michigan Medical School, M5240 Medical Science I Bldg, 1301 Catherine Rd, Ann Arbor, MI 48109 0602, USA
    Eur Respir J Suppl 44:22s-23s. 2003
  28. pmc Do MDL-1⁺ cells play a broad role in acute inflammation?
    Peter A Ward
    University of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan, USA
    J Clin Invest 121:4234-7. 2011
    ..These findings may have broad mechanistic and therapeutic implications for the development of SIRS, sepsis, and shock in humans exposed to a wide array of infectious and non-infectious conditions...
  29. pmc MyD88-dependent production of IL-17F is modulated by the anaphylatoxin C5a via the Akt signaling pathway
    Markus Bosmann
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    FASEB J 25:4222-32. 2011
    ..A similar result was found in the cecal ligation and puncture sepsis model. These data suggest that maximal production of IL-17F requires complement activation and presence of C5a...
  30. doi request reprint Oxidative stress: acute and progressive lung injury
    Peter A Ward
    University of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan, USA
    Ann N Y Acad Sci 1203:53-9. 2010
    ..How residential or circulating stem cells participate in regeneration of damaged/destroyed cells may provide clues regarding therapy in humans who are experiencing lung inflammatory damage...
  31. pmc The harmful role of c5a on innate immunity in sepsis
    Peter A Ward
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 5602, USA
    J Innate Immun 2:439-45. 2010
    ..Collectively, these findings suggest that interception of C5a in sepsis preserves innate immune functions and may be a strategy for treatment of septic humans...
  32. ncbi request reprint A key role of C5a/C5aR activation for the development of sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109 0602, USA
    J Leukoc Biol 74:966-70. 2003
    ..This review article provides an overview of the important role of C5a/C5aR activation for the onset and development of sepsis...
  33. pmc Sepsis, complement and the dysregulated inflammatory response
    Peter A Ward
    The University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109 5602, USA
    J Cell Mol Med 13:4154-60. 2009
    ..These findings may have implications for therapeutic interventions in human beings with sepsis...
  34. ncbi request reprint Evidence for a functional role of the second C5a receptor C5L2
    Hongwei Gao
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    FASEB J 19:1003-5. 2005
    ..When normal blood neutrophils were stimulated in vitro with LPS and C5a, the antibodies had similar effects on release of IL-6. These data provide the first evidence for a role for C5L2 in balancing the biological responses to C5a...
  35. ncbi request reprint Complement-induced impairment of innate immunity during sepsis
    Markus S Huber-Lang
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 169:3223-31. 2002
    ..These data identify a molecular basis for defective innate immunity involving neutrophils during sepsis...
  36. pmc Regulatory effects of iNOS on acute lung inflammatory responses in mice
    Cecilia L Speyer
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Am J Pathol 163:2319-28. 2003
    ..It appears that iNOS affects the lung inflammatory response by regulating chemokine production...
  37. ncbi request reprint Altered neutrophil trafficking during sepsis
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    J Immunol 169:307-14. 2002
    ..These data suggest that sepsis causes enhanced neutrophil trafficking into the lung via mechanisms that are not engaged in the nonseptic state...
  38. pmc Novel chemokine responsiveness and mobilization of neutrophils during sepsis
    Cecilia L Speyer
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    Am J Pathol 165:2187-96. 2004
    ..These findings suggest that sepsis fundamentally alters the trafficking of PMN into the lung in a manner that now engages functional responses to CC chemokines...
  39. pmc Relationship of acute lung inflammatory injury to Fas/FasL system
    Thomas A Neff
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 0602, USA
    Am J Pathol 166:685-94. 2005
    ..These data suggest that the Fas/FasL system regulates the acute lung inflammatory response by positively affecting CXC-chemokine production, ultimately leading to enhanced neutrophil influx and tissue damage...
  40. doi request reprint Adverse functions of IL-17A in experimental sepsis
    Michael A Flierl
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 0602, USA
    FASEB J 22:2198-205. 2008
    ..IL-17A may be a potential therapeutic target in sepsis...
  41. ncbi request reprint Adenoviral-mediated overexpression of SOCS3 enhances IgG immune complex-induced acute lung injury
    Hongwei Gao
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    J Immunol 177:612-20. 2006
    ..In vitro, SOCS3 overexpression abrogated IL-6-induced activation of STAT3 in lung epithelial cells. These findings suggest SOCS3 is an important regulator of lung inflammatory injury after deposition of IgG IC...
  42. pmc Functional roles for C5a receptors in sepsis
    Daniel Rittirsch
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109, USA
    Nat Med 14:551-7. 2008
    ..Thus, contrary to earlier speculation, C5l2 is a functional receptor rather than merely a default receptor...
  43. ncbi request reprint Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109 0602, USA
    FASEB J 18:370-2. 2004
    ..Accordingly, we suggest that induction of IL-6 after CLP is neutrophil and C5a/C5aR dependent, likely due to the ability of C5a to cause activation of ERK1/2 and p38 MAPK signaling pathways...
  44. ncbi request reprint Expression and function of the C5a receptor in rat alveolar epithelial cells
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 168:1919-25. 2002
    ..The functional outcome is enhanced release of proinflammatory mediators. These data underscore the phlogistic potential of RAEC and the ability of C5a to enhance the phlogistic responses of RAEC...
  45. pmc Acute lung injury induced by lipopolysaccharide is independent of complement activation
    Daniel Rittirsch
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 180:7664-72. 2008
    ..Most strikingly, complement activation does not contribute to the development of ALI in the LPS model...
  46. ncbi request reprint Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    J Immunol 170:503-7. 2003
    ....
  47. pmc Activator protein-1 activation in acute lung injury
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Am J Pathol 161:275-82. 2002
    ..The data suggest that activation of AP-1 occurs in both alveolar macrophages and in the lung, and this activation process is macrophage- and tumor necrosis factor-alpha-dependent...
  48. ncbi request reprint Expression and function of C5a receptor in mouse microvascular endothelial cells
    Ines J Laudes
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 169:5962-70. 2002
    ....
  49. ncbi request reprint Regulatory effects of estrogen on acute lung inflammation in mice
    Cecilia L Speyer
    Dept of Pathology, Univ of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109 0602, USA
    Am J Physiol Cell Physiol 288:C881-90. 2005
    ..These data suggest that estrogen suppresses lung inflammatory responses in mice through an effect on vascular cell adhesion molecules and proinflammatory mediators...
  50. doi request reprint Ability of antioxidant liposomes to prevent acute and progressive pulmonary injury
    Laszlo M Hoesel
    Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    Antioxid Redox Signal 10:973-81. 2008
    ..Accordingly, the liposomal strategy may be therapeutically useful in CEES-induced lung injury in humans...
  51. ncbi request reprint Protection of innate immunity by C5aR antagonist in septic mice
    Markus S Huber-Lang
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    FASEB J 16:1567-74. 2002
    ..These data suggest that C5aRa interferes with neutrophil responses to C5a, preventing C5a-induced compromise of innate immunity during sepsis, with greatly improved survival rates after CLP...
  52. pmc Attenuation of IgG immune complex-induced acute lung injury by silencing C5aR in lung epithelial cells
    Lei Sun
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109 5602, USA
    FASEB J 23:3808-18. 2009
    ....
  53. ncbi request reprint Role of C5a-C5aR interaction in sepsis
    Ren Feng Guo
    University of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan 48109 0602, USA
    Shock 21:1-7. 2004
    ..These data suggest that in sepsis C5a-C5aR signaling is excessive, resulting in paralysis of neutrophil function. Interception of either C5a or C5aR dramatically improves survival during experimental sepsis...
  54. ncbi request reprint Stat3 activation in acute lung injury
    Hongwei Gao
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109 0602, USA
    J Immunol 172:7703-12. 2004
    ..These data suggest in the lung injury model used that activation of Stat3 in lungs is macrophage dependent and neutrophil dependent. IL-6, IL-10, and C5a contribute to Stat3 activation in inflamed rat lung...
  55. pmc Increased C5a receptor expression in sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    J Clin Invest 110:101-8. 2002
    ..These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis...
  56. ncbi request reprint Phagocyte-derived catecholamines enhance acute inflammatory injury
    Michael A Flierl
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 449:721-5. 2007
    ..We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response...
  57. ncbi request reprint Regulation by C5a of neutrophil activation during sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Immunity 19:193-202. 2003
    ..These data suggest that CLP-induced sepsis causes a C5a-dependent dysfunction of neutrophils, which is characterized by altered signaling associated with NF-kappaB activation...
  58. pmc Harmful molecular mechanisms in sepsis
    Daniel Rittirsch
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109 0602, USA
    Nat Rev Immunol 8:776-87. 2008
    ..In this Review, we highlight recent insights into the molecular interactions that occur during sepsis and attempt to unravel the nature of the dysregulated immune response during sepsis...
  59. ncbi request reprint C5a receptor and thymocyte apoptosis in sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    FASEB J 16:887-8. 2002
    ..These data provide the first direct evidence that in the early onset of sepsis, increased expression of C5aR occurs in thymocytes, which increases their susceptibility to C5a-induced apoptosis...
  60. ncbi request reprint Mediators and regulation of neutrophil accumulation in inflammatory responses in lung: insights from the IgG immune complex model
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    Free Radic Biol Med 33:303-10. 2002
    ..In this review, we focus on the current knowledge of the mechanisms leading to accumulation of neutrophils during acute lung injury...
  61. pmc Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury
    Mark R Hemmila
    Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109 5033, USA
    Surgery 148:499-509. 2010
    ..In addition to reducing infection, nanoemulsion therapy may modulate dermal inflammatory signaling and thereby lessen inflammation following thermal injury...
  62. pmc Generation of C5a by phagocytic cells
    Markus Huber-Lang
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA
    Am J Pathol 161:1849-59. 2002
    ..These data indicate that phagocytic cells, especially lung macrophages, can generate C5a from C5. In the context of the lung, this may represent an important C5a-generating pathway that is independent of the plasma complement system...
  63. ncbi request reprint Attenuation of half sulfur mustard gas-induced acute lung injury in rats
    Shannon D McClintock
    The University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA
    J Appl Toxicol 26:126-31. 2006
    ..These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes...
  64. ncbi request reprint Murine complement interactions with Pseudomonas aeruginosa and their consequences during pneumonia
    John G Younger
    Department of Emergency Medicine, Division of Pulmonary and Critical Care Medicine, Univeristy of Michigan, Ann Arbor, MI 48109 0303
    Am J Respir Cell Mol Biol 29:432-8. 2003
    ..This interaction in vivo plays a central role in host survival beyond just recruitment and activation of phagocytes and may serve to limit the inflammatory response to and tissue injury resulting from bacterial infection...
  65. ncbi request reprint Protection from half-mustard-gas-induced acute lung injury in the rat
    Shannon D McClintock
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109 0602, USA
    J Appl Toxicol 22:257-62. 2002
    ....
  66. ncbi request reprint Exogenous nitric oxide donor and related compounds protect against lung inflammatory response after hemorrhagic shock and resuscitation
    Roberto Anaya-Prado
    Borgess Research Institute, Trauma, Surgery Research Sciences and Molecular Biology, the Departments of Surgery and Research, Michigan State University Kalamazoo Center for Medical Studies, Kalamazoo, Michigan, USA
    J Trauma 57:980-8. 2004
    ....
  67. ncbi request reprint Divergent signaling pathways in phagocytic cells during sepsis
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    J Immunol 177:1306-13. 2006
    ..As a result, CXC chemokines increase in lung, setting the stage for neutrophil accumulation in lung during sepsis...
  68. ncbi request reprint Selectin inhibition modulates NF-kappa B and AP-1 signaling after liver ischemia/reperfusion
    Luis H Toledo-Pereyra
    Borgess Research Institute, Trauma, Surgery Research Sciences, and Molecular Biology, Michigan State University, East Lansing, Michigan, USA
    J Invest Surg 19:313-22. 2006
    ..There was dissociation in the activation signals of NF-kappa B and AP-1. Increase in NF-kappa B and reduction of the activation of AP-1 were noted at 3 h of reperfusion...
  69. ncbi request reprint In vivo regulation of neutrophil apoptosis by C5a during sepsis
    Ren Feng Guo
    University of Michigan Medical School, Department of Pathology, 1301 Catherine Road, Ann Arbor, MI 48109 0602, USA
    J Leukoc Biol 80:1575-83. 2006
    ..Thus, neutrophil survival signals derived from effects of septic sera could be linked to activation of ERK1/2 and PI-3K, increased antiapoptotic protein expression, and ultimately, delayed neutrophil apoptosis...
  70. ncbi request reprint Role of oxidants in lung injury during sepsis
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Antioxid Redox Signal 9:1991-2002. 2007
    ..However, the results are inconclusive. In this article, we focus on the current understanding of the pathogenesis of sepsis-induced ALI and novel antioxidant strategies for therapeutic purposes...
  71. ncbi request reprint In vivo biological responses in the presence or absence of C3
    J Vidya Sarma
    The University of Michigan Medical School, Department of Pathology, 1150 West Medical Center Drive Ann Arbor, MI 48109 0602, USA
    Adv Exp Med Biol 598:240-50. 2007
  72. ncbi request reprint Regulation of lung inflammation in the model of IgG immune-complex injury
    Hongwei Gao
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Annu Rev Pathol 1:215-42. 2006
    ..Insights into potential interventional approaches for the suppression of inflammatory processes in humans have emerged from those studies...
  73. ncbi request reprint C5a, a therapeutic target in sepsis
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Recent Pat Antiinfect Drug Discov 1:57-65. 2006
    ..This review will summarize the beneficial effects of anti-C5a treatment in the rodent model of sepsis and will introduce the most recent patents on this line of research...
  74. ncbi request reprint Role of C5a in inflammatory responses
    Ren Feng Guo
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0602, USA
    Annu Rev Immunol 23:821-52. 2005
    ..Herein, we review human and animal data describing the cellular and molecular mechanisms of C5a in the development of inflammatory disorders, sepsis, acute lung injury, ischemia-reperfusion injury, and asthma...
  75. ncbi request reprint Harmful and protective roles of neutrophils in sepsis
    Laszlo M Hoesel
    Department of Pathologycine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Shock 24:40-7. 2005
    ....
  76. pmc Functions of the complement components C3 and C5 during sepsis
    Michael A Flierl
    Dept of Pathology, University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, MI 48109, USA
    FASEB J 22:3483-90. 2008
    ..Thus, during sepsis, blockade of C5a or its receptors (rather than C5) seems a more promising strategy, because C5a-blockade still allows for MAC formation while the adverse effects of C5a are prevented...
  77. pmc Immunodesign of experimental sepsis by cecal ligation and puncture
    Daniel Rittirsch
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109, USA
    Nat Protoc 4:31-6. 2009
    ..The CLP procedure can be performed in as little as 10 min for each animal by an experienced user, with additional time required for subsequent postoperative care and data collection...
  78. ncbi request reprint Regulatory role of C5a on macrophage migration inhibitory factor release from neutrophils
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 173:1355-9. 2004
    ..Our data suggest that C5a plays a role in enhancing MIF release from neutrophils in vitro and during sepsis. These findings represent a previously unrecognized function of C5a and neutrophils in the appearance of MIF in sepsis...
  79. ncbi request reprint Neutrophil C5a receptor and the outcome in a rat model of sepsis
    Ren Feng Guo
    Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd, Ann Arbor, Michigan 48109 0602, USA
    FASEB J 17:1889-91. 2003
    ..These data suggest that neutrophil C5aR content represents an essential component of an efficient defense system in sepsis and may serve as a prognostic marker for the outcome...
  80. ncbi request reprint C5a-blockade improves burn-induced cardiac dysfunction
    Laszlo M Hoesel
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    J Immunol 178:7902-10. 2007
    ..These results suggest a linkage between C5a and burn-induced cardiac dysfunction and a possible contribution of LPS to these events...
  81. pmc Complement dependency of cardiomyocyte release of mediators during sepsis
    Gelareh Atefi
    The University of Michigan Medical School, Department of Pathology, 1301 Catherine Rd Box 5602, Ann Arbor, MI 48109 5602, USA
    FASEB J 25:2500-8. 2011
    ..These data may be relevant to a strategy for the treatment of heart dysfunction developing during sepsis...
  82. ncbi request reprint Generation of C5a in the absence of C3: a new complement activation pathway
    Markus Huber-Lang
    Department of Traumatology, Hand and Reconstructive Surgery, University of Ulm Medical School, Steinhoevelstrasse 9, D 89075 Ulm, Germany
    Nat Med 12:682-7. 2006
    ..These data suggest that, in the genetic absence of C3, thrombin substitutes for the C3-dependent C5 convertase. This linkage between the complement and coagulation pathways may represent a new pathway of complement activation...
  83. ncbi request reprint Multiple selectin blockade with a small-molecule selectin inhibitor does not affect survival after a second inflammatory challenge with nonlethal LPS
    Roberto Anaya-Prado
    Borgess Research Institute, Trauma, Surgery Research Sciences, and Molecular Biology, Kalamazoo, Michigan 49048, USA
    J Invest Surg 15:171-80. 2002
    ..We conclude that TBC-1269, multisectin blocker, was effective in reducing liver damage even with the addition of a second inflammatory insult as the nonlethal LPS challenge used in this study...
  84. ncbi request reprint The phosphatidylinositol 3-kinase signaling pathway exerts protective effects during sepsis by controlling C5a-mediated activation of innate immune functions
    Christiane D Wrann
    Department of Trauma Surgery, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    J Immunol 178:5940-8. 2007
    ..Our data suggest that the PI3K/Akt signaling pathway controls various C5a-mediated effects on neutrophil and monocyte innate immunity and exerts an overall protective effect during experimental sepsis...
  85. ncbi request reprint Role of nitric oxide in acute lung inflammation: lessons learned from the inducible nitric oxide synthase knockout mouse
    Thomas P Shanley
    Division of Critical Care Medicine, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Crit Care Med 30:1960-8. 2002
    ..These results and other previous investigations have been complicated by the use of nonselective blockers of the iNOS isoform...
  86. ncbi request reprint Exogenous nitric oxide downregulates MIP-2 and MIP-1alpha chemokines and MAPK p44/42 after ischemia and reperfusion of the rat kidney
    Gustavo Martinez-Mier
    Department of Surgery Research Sciences, Trauma and Molecular Biology, Borgess Research Institute, Kalamazoo, Michigan 49001, USA
    J Invest Surg 15:287-96. 2002
    ..Exogenous NO had a temporal protective effect in organ function and histology and exerted a downregulating response in the production of MIP-2 and MIP-1alpha chemokines and the activation of MAPK p44/42 following I/R...
  87. ncbi request reprint A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome
    Armin Gerbitz
    Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany
    Transplantation 79:536-42. 2005
    ..EC expression of the adhesion molecule CD54 (intercellular adhesion molecule [ICAM]-1) has been shown to be a major regulator of pulmonary inflammation in various experimental models...
  88. ncbi request reprint Agonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophils
    Victoria M Shpacovitch
    Department of Dermatology, IZKF Münster, and Boltzmann Institute for Immunobiology of the Skin, University of Munster, Germany
    Exp Dermatol 16:799-806. 2007
    ....
  89. ncbi request reprint Inflammatory response of tracheobronchial epithelial cells to endotoxin
    Simona B Neff
    Institute of Anesthesiology, University of Zurich Medical School, Zurich, Switzerland
    Am J Physiol Lung Cell Mol Physiol 290:L86-96. 2006
    ..01). These data provide evidence that LPS induces TBEC killing in a necrosis- and apoptosis-dependent manner...
  90. ncbi request reprint Regulatory role of IL-10 in experimental obliterative bronchiolitis in rats
    Babu Naidu
    Department of Cardiothoracic Surgery, University of Washington Medical School, Seattle, Washington 98115, USA
    Exp Mol Pathol 73:164-70. 2002
    ..These findings suggest that endogenous IL-10 plays a regulatory role in the development of experimental OB...
  91. ncbi request reprint Oxidized lipid protects against sepsis
    Niels C Riedemann
    Nat Med 8:1084-5. 2002
  92. ncbi request reprint Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans
    Markus Huber-Lang
    Department of Traumatology, Hand and Reconstructive Surgery, University of Ulm Medical School, Germany
    J Immunol 174:1104-10. 2005
    ..In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on PMN diminishes during sepsis due to systemic generation of C5a, which is associated with a poor prognosis...

Research Grants28

  1. Regulation of Lung Inflammation by Catecholamines and Adrenergic Receptors
    Peter A Ward; Fiscal Year: 2010
    ..The proposed work will relate to our recent discoveries that the adrenergic nervous system plays an important role in acute lung inflammation and can be manipulated for therapeutic benefit. ..
  2. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2005
    ..Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. ..
  3. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2005
    ..We expect that these studies will provide important information on pro-inflammatory and anti-inflammatory cascades in lung and the roles of C5aR and C5L2 in the lung inflammatory response. ..
  4. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2002
    ..Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. ..
  5. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2003
    ..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
  6. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2006
    ..The unifying theme in these studies is sepsis-induced production of C5a which, interacting with its receptors, results in highly destructive outcomes. ..
  7. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2007
    ..We expect that these studies will provide important information on pro-inflammatory and anti-inflammatory cascades in lung and the roles of C5aR and C5L2 in the lung inflammatory response. ..
  8. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2007
    ..The unifying theme in these studies is sepsis-induced production of C5a which, interacting with its receptors, results in highly destructive outcomes. ..
  9. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2009
    ..The unifying theme in these studies is sepsis-induced production of C5a which, interacting with its receptors, results in highly destructive outcomes. ..
  10. Protective Effects of Anti-C5a in Sepsis
    Peter A Ward; Fiscal Year: 2010
    ..It is clear that we have incomplete understanding of sepsis. Until this obstacle is resolved through an understanding of the molecular determinants of sepsis, treatment will be supportive and extremely costly. ..
  11. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2004
    ..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
  12. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2006
    ..We expect that these studies will provide important information on pro-inflammatory and anti-inflammatory cascades in lung and the roles of C5aR and C5L2 in the lung inflammatory response. ..
  13. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2004
    ..Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. ..
  14. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 1999
    ..A thermal injury model will be used to evaluate the role of C5a and C6-dependent products in local and remote organ injury, as part of an effort to understand systemic inflammatory responses (Aim 6). ..
  15. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2002
    ..Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. ..
  16. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2002
    ..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
  17. Protective Effects of Anti-C5a in Sepsis
    Peter Ward; Fiscal Year: 2003
    ..Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. ..
  18. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2001
    ..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
  19. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2000
    ..A thermal injury model will be used to evaluate the role of C5a and C6-dependent products in local and remote organ injury, as part of an effort to understand systemic inflammatory responses (Aim 6). ..