Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology

Summary

Principal Investigator: CHRISTINA CARROLL LESLIE
Abstract: There is immense potential to generate a variety of bioactive lipids in the lung in response to injury and infection. The central theme of this proposal is that lipid mediators have diverse functions in controlling the amplitude of the inflammatory response and its resolution. Our goals are to define the role of specific lipid mediators in protecting the lung during inflammatory injury and infection, and to determine how the environmental toxicant ozone induces production of novel lipid metabolites that interfere with these processes leading to pathological consequences. The objectives are to: Elucidate mechanisms of Group IVA cytosolic phospholipase A2 activation and eicosanoid production in resident peritoneal and alveolar macrophages by Cantjida albicans and Aspergillus fumigatus, and determine the role of this pathway in regulating immune responses to fungal infection in the lung. Define the mechanisms of production of the novel lipid mediator lysophosphatidylserine by neutrophils and macrophages, and determine how it mediates the removal of apoptotic cells and suppresses pro-inflammatory cytokine production to promote the resoiution of lung inflammation. Structurally characterize by mass spectrometry novel lipid mediators produced following exposure of lung surfactant to low levels of ozone, and to determine their impact on the ability of the lung to control inflammation and infection. Novel mass spectrometry approaches will be developed to image these lipid mediators in ozonized lung tissues. This program brings together investigators with diverse expertise in cell biology, biochemistry and structural biology. By using multidisciplinary approaches, we will determine the structural identity of lipid mediators, the molecular mechanisms involved in their production and how they function to regulate lung responses.
Funding Period: 1997-09-01 - 2016-01-31
more information: NIH RePORT

Top Publications

  1. pmc Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry
    Karin A Zemski Berry
    Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045 and
    J Lipid Res 55:504-15. 2014
  2. pmc IgG autoantibodies against deposited C3 inhibit macrophage-mediated apoptotic cell engulfment in systemic autoimmunity
    Karla D Kenyon
    Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Immunol 187:2101-11. 2011
  3. pmc Neutrophil clearance: when the party is over, clean-up begins
    Donna L Bratton
    National Jewish Health, 1400 Jackson Street, Room A540, Denver, CO 80206, USA
    Trends Immunol 32:350-7. 2011
  4. pmc Signaling via macrophage G2A enhances efferocytosis of dying neutrophils by augmentation of Rac activity
    S Courtney Frasch
    Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Biol Chem 286:12108-22. 2011
  5. pmc Disruption of contact lens-associated Pseudomonas aeruginosa biofilms formed in the presence of neutrophils
    Danielle M Robertson
    Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9057, USA
    Invest Ophthalmol Vis Sci 52:2844-50. 2011
  6. pmc Pulmonary surfactant phosphatidylglycerol inhibits Mycoplasma pneumoniae-stimulated eicosanoid production from human and mouse macrophages
    Pitchaimani Kandasamy
    Department of Medicine, National Jewish Health, Denver, Colorado, 80206, USA
    J Biol Chem 286:7841-53. 2011
  7. ncbi Activation of group IVC phospholipase A(2) by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells
    Patricia K Tithof
    Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 4545, USA
    Arch Toxicol 85:623-34. 2011
  8. pmc Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress
    Angela K Tollefson
    Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    Free Radic Biol Med 49:1937-46. 2010
  9. ncbi Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner
    Ruby Fernandez-Boyanapalli
    National Jewish Health, Denver, CO 80206, USA
    J Immunol 185:4030-41. 2010
  10. pmc Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms
    Farideh Ghomashchi
    Department of Chemistry, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 285:36100-11. 2010

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
  2. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013

Detail Information

Publications59

  1. pmc Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry
    Karin A Zemski Berry
    Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045 and
    J Lipid Res 55:504-15. 2014
    ....
  2. pmc IgG autoantibodies against deposited C3 inhibit macrophage-mediated apoptotic cell engulfment in systemic autoimmunity
    Karla D Kenyon
    Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Immunol 187:2101-11. 2011
    ..We propose that the suppression of apoptotic cell disposal by Abs against deposited C3 may contribute to increasing severity and/or exacerbations in SLE...
  3. pmc Neutrophil clearance: when the party is over, clean-up begins
    Donna L Bratton
    National Jewish Health, 1400 Jackson Street, Room A540, Denver, CO 80206, USA
    Trends Immunol 32:350-7. 2011
    ..If not removed, dying neutrophils disintegrate and release phlogistic cargo that can further contribute to ongoing inflammation, tissue destruction, or autoimmunity...
  4. pmc Signaling via macrophage G2A enhances efferocytosis of dying neutrophils by augmentation of Rac activity
    S Courtney Frasch
    Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    J Biol Chem 286:12108-22. 2011
    ..Together, these data support the hypothesis that lyso-PS presented on the surface of activated and dying neutrophils provides a tightly controlled, proresolution signal for high capacity clearance of neutrophils in acute inflammation...
  5. pmc Disruption of contact lens-associated Pseudomonas aeruginosa biofilms formed in the presence of neutrophils
    Danielle M Robertson
    Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9057, USA
    Invest Ophthalmol Vis Sci 52:2844-50. 2011
    ..Agents that target F-actin and DNA were tested as a therapeutic strategy for disrupting biofilms formed in the setting of neutrophils in vitro and for limiting the infectious bioburden in vivo...
  6. pmc Pulmonary surfactant phosphatidylglycerol inhibits Mycoplasma pneumoniae-stimulated eicosanoid production from human and mouse macrophages
    Pitchaimani Kandasamy
    Department of Medicine, National Jewish Health, Denver, Colorado, 80206, USA
    J Biol Chem 286:7841-53. 2011
    ..pneumoniae-induced AA release. Collectively, these data demonstrate that M. pneumoniae stimulates the production of eicosanoids from macrophages through TLR2, and POPG suppresses this pathogen-induced response...
  7. ncbi Activation of group IVC phospholipase A(2) by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells
    Patricia K Tithof
    Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 4545, USA
    Arch Toxicol 85:623-34. 2011
    ..These data suggest that PAHs induce apoptosis of HCAECs via activation of group IVC PLA(2)...
  8. pmc Endogenous enzymes (NOX and ECSOD) regulate smoke-induced oxidative stress
    Angela K Tollefson
    Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    Free Radic Biol Med 49:1937-46. 2010
    ..These data suggest that the mechanisms underlying the host defense against cigarette smoke-induced oxidative damage and subsequent development of COPD may include endogenous oxidases and antioxidant enzymes...
  9. ncbi Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner
    Ruby Fernandez-Boyanapalli
    National Jewish Health, Denver, CO 80206, USA
    J Immunol 185:4030-41. 2010
    ..These data support the hypothesis that in addition to correcting immunodeficiency in CGD, IFN-γ priming of Ms restores clearance of apoptotic cells and may thereby contribute to resolution of exaggerated CGD inflammation...
  10. pmc Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms
    Farideh Ghomashchi
    Department of Chemistry, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 285:36100-11. 2010
    ..This led to the discovery of a potent and selective inhibitor of mouse cPLA(2)β. These in vitro studies help determine the regulation and function of the cPLA(2) family members...
  11. pmc PPARγ activation normalizes resolution of acute sterile inflammation in murine chronic granulomatous disease
    Ruby Fernandez-Boyanapalli
    Department of Pediatrics, National Jewish Health, Denver, CO, USA
    Blood 116:4512-22. 2010
    ..As such, PPARγ may be a therapeutic target for CGD, and possibly other inflammatory conditions where aberrant macrophage programming and impaired efferocytosis delay resolution of inflammation...
  12. pmc Pathways regulating cytosolic phospholipase A2 activation and eicosanoid production in macrophages by Candida albicans
    Saritha Suram
    Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA
    J Biol Chem 285:30676-85. 2010
    ..The results demonstrate that C. albicans engages both β-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA(2)α and eicosanoid production...
  13. pmc Group IVA phospholipase A₂ is necessary for growth cone repulsion and collapse
    Staci D Sanford
    Department of Pediatrics, Neuroscience Program, and Colorado Intellectual and Developmental Disabilities Research Center, University of Colorado School of Medicine, Aurora, Colorado, USA
    J Neurochem 120:974-84. 2012
    ..These studies identify a novel, early step in Sema3A-signaling and a PLA(2) necessary for growth cone repulsion and collapse...
  14. pmc Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity
    Yongxue Yao
    Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 287:9311-21. 2012
    ..These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity...
  15. pmc Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells
    Mark T Kearns
    National Jewish Health, Denver, CO 80206, USA
    Am J Physiol Lung Cell Mol Physiol 302:L711-8. 2012
    ..These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance...
  16. pmc Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation
    Bogeon Yun
    From the Department of Pediatrics, National Jewish Health, Denver, Colorado 80206
    J Biol Chem 289:1491-504. 2014
    ..This work reveals the potential for development of small molecule cell-permeable serine hydrolase inhibitors that block MCU-mediated mitochondrial calcium overload, MPTP formation, and necrotic cell death. ..
  17. pmc Cytosolic phospholipase A(2)α and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation
    Saritha Suram
    Department of Pediatrics, National Jewish Health, Denver, CO, USA
    PLoS ONE 8:e69002. 2013
    ..albicans stimulates an autocrine loop in macrophages involving cPLA2α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation. ..
  18. pmc Induction of TGF-β1 synthesis by macrophages in response to apoptotic cells requires activation of the scavenger receptor CD36
    Weipeng Xiong
    Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America
    PLoS ONE 8:e72772. 2013
    ..However, the PS receptor(s) responsible for this induction has not been clearly determined...
  19. pmc Human platelets generate phospholipid-esterified prostaglandins via cyclooxygenase-1 that are inhibited by low dose aspirin supplementation
    Maceler Aldrovandi
    Institute of Infection and Immunity, School of Medicine, Cardiff University
    J Lipid Res 54:3085-97. 2013
    ..In summary, COX-1 in human platelets acutely mediates membrane phospholipid oxidation via formation of PG-esterified PLs in response to pathophysiological agonists...
  20. pmc Antiinflammatory effects of apoptotic cells
    Peter M Henson
    Program in Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
    J Clin Invest 123:2773-4. 2013
    ..Here they discuss the evolving relationship among apoptosis, phagocytosis, and inflammation. ..
  21. pmc Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival
    Kenneth C Malcolm
    Department of Medicine, National Jewish Health, Denver, Colorado, United States of America
    PLoS ONE 8:e57402. 2013
    ..aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy...
  22. pmc Neutrophils regulate tissue Neutrophilia in inflammation via the oxidant-modified lipid lysophosphatidylserine
    S Courtney Frasch
    Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA
    J Biol Chem 288:4583-93. 2013
    ....
  23. pmc Obesity impairs apoptotic cell clearance in asthma
    Ruby Fernandez-Boyanapalli
    Department of Pediatrics, National Jewish Health, University of Colorado School of Medicine, Denver, CO 80206, USA
    J Allergy Clin Immunol 131:1041-7, 1047.e1-3. 2013
    ..Asthma in obese adults is typically more severe and less responsive to glucocorticoids than asthma in nonobese adults...
  24. pmc Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes
    Ramaprasad Talahalli
    Rainbow Babies and Children s Hospital, 11100 Euclid Ave, Cleveland, OH 44106, USA
    J Leukoc Biol 93:135-43. 2013
    ..05). Our data suggest the critical involvement of leukocytes and LTs in the regulation of inflammation and capillary degeneration in DR...
  25. pmc Modulation of macrophage efferocytosis in inflammation
    Darlynn Korns
    Division of Cell Biology, Department of Pediatrics, National Jewish Health Denver, CO, USA
    Front Immunol 2:57. 2011
    ..This review summarizes the current knowledge of the multiple factors that modulate macrophage efferocytic ability and highlights emerging therapeutic targets with significant potential for limiting chronic inflammation...
  26. pmc Emerging roles for lysophosphatidylserine in resolution of inflammation
    S Courtney Frasch
    Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    Prog Lipid Res 51:199-207. 2012
    ..This article will review our current knowledge of lysoPS biology including receptor signaling and mechanisms of generation as well as summarize the more recent evidence of its expanding roles in inflammation...
  27. pmc Phospholipase A2IVα regulates phagocytosis independent of its enzymatic activity
    Pasquale Zizza
    Institute of Protein Biochemistry, National Research Council, Via Pietro Castellino 111, 80131 Naples, Italy
    J Biol Chem 287:16849-59. 2012
    ..These data unveil a new mechanism of action for PLA(2)IVα, which demonstrates that the membrane binding, and not the enzymatic activity, is required for PLA(2)IVα modulation of FcR-mediated phagocytosis...
  28. ncbi Characterization of oxidized phosphatidylethanolamine derived from RAW 264.7 cells using 4-(dimethylamino)benzoic acid derivatives
    Karin A Zemski Berry
    Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA
    Eur J Mass Spectrom (Chichester, Eng) 16:463-70. 2010
    ..The stable isotope labeled derivatives permitted assessment of relative quantitative changes in oxidized lipids based upon ion abundance...
  29. pmc Stable isotope labeled 4-(dimethylamino)benzoic acid derivatives of glycerophosphoethanolamine lipids
    Karin A Zemski Berry
    Department of Pharmacology, University of Colorado Denver, Aurora, Colorado 80045, USA
    Anal Chem 81:6633-40. 2009
    ..These DMABA NHS ester reagents provide a universal scan for diacyl, ether, and plasmalogen PE lipids that cannot be readily observed otherwise, enable differential labeling, and provide an internal standard for each PE lipid...
  30. pmc Localization and function of cytosolic phospholipase A2alpha at the Golgi
    Christina C Leslie
    Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
    Biochimie 92:620-6. 2010
    ..Thus, there is continued need for studies employing highly specific cPLA(2)alpha antagonists in addition to genetic deletion of cPLA(2)alpha in mice...
  31. pmc Sublimation as a method of matrix application for mass spectrometric imaging
    Joseph A Hankin
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045 0511, USA
    J Am Soc Mass Spectrom 18:1646-52. 2007
    ..This inexpensive method was reproducible and eliminated the potential for spreading of analytes arising from solvent deposition during matrix application...
  32. pmc Characterization of acrolein-glycerophosphoethanolamine lipid adducts using electrospray mass spectrometry
    Karin A Zemski Berry
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Chem Res Toxicol 20:1342-51. 2007
    ....
  33. ncbi TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic phospholipase A2 and oxidant-dependent mechanisms
    Kathleen McPhillips
    Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 178:8117-26. 2007
    ..Overall, the data suggest that macrophages in a TNF-alpha- and oxidant-rich inflammatory environment are less able to remove apoptotic cells and, thereby, may contribute to the local intensity of the inflammatory response...
  34. ncbi Lysophospholipids of different classes mobilize neutrophil secretory vesicles and induce redundant signaling through G2A
    S Courtney Frasch
    Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 178:6540-8. 2007
    ..Together, these data show that lyso-PLs bearing various head groups redundantly mobilize G2A latent within secretory vesicles and result in G2A receptor/Galphai/phospholipase C signaling for calcium flux in neutrophils...
  35. pmc Function, activity, and membrane targeting of cytosolic phospholipase A(2)zeta in mouse lung fibroblasts
    Moumita Ghosh
    Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Biol Chem 282:11676-86. 2007
    ....
  36. ncbi Properties of the Group IV phospholipase A2 family
    Moumita Ghosh
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Prog Lipid Res 45:487-510. 2006
    ..Current information available about the biochemical properties and tissue distribution of other Group IV PLA2s suggests they may have distinct mechanisms of regulation and functional roles...
  37. ncbi Recognition ligands on apoptotic cells: a perspective
    Shyra J Gardai
    Division of Pulmonary and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
    J Leukoc Biol 79:896-903. 2006
    ..Loss or inactivation of the don't eat me CD47 effects accompanies apoptosis and now allow the cells to be recognized and cleared...
  38. ncbi Identification of the expressed form of human cytosolic phospholipase A2beta (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early endosomes
    Moumita Ghosh
    Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    J Biol Chem 281:16615-24. 2006
    ..cPLA(2)beta3 is widely expressed in tissues, suggesting that it has a generalized function at these unique sites...
  39. pmc Group V secretory phospholipase A2 translocates to the phagosome after zymosan stimulation of mouse peritoneal macrophages and regulates phagocytosis
    Barbara Balestrieri
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:6691-8. 2006
    ..These data demonstrate that group V sPLA2 contributes to the innate immune response both through regulation of eicosanoid generation in response to a phagocytic stimulus and also as a component of the phagocytic machinery...
  40. ncbi Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor
    Saritha Suram
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Biol Chem 281:5506-14. 2006
    ....
  41. ncbi Oxidants selectively reverse TGF-beta suppression of proinflammatory mediator production
    Yi Qun Xiao
    Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 176:1209-17. 2006
    ..This was mediated through Src tyrosine kinases and protein phosphatase-1/2A. By contrast, hydrogen peroxide had no effects on TGF-beta-induced Smad2 phosphorylation and SBE-luc reporter gene transcription...
  42. ncbi Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2
    Shahid Noor
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Biol Chem 283:4744-55. 2008
    ..Therefore activation of cPLA2alpha in macrophages may impact immune responses to L. monocytogenes...
  43. pmc Cholesterol, reactive oxygen species, and the formation of biologically active mediators
    Robert C Murphy
    Department of Pharmacology, University of Colorado Denver Health Sciences Center, Aurora, Colorado 80045 6511, USA
    J Biol Chem 283:15521-5. 2008
  44. pmc Novel translocation responses of cytosolic phospholipase A2alpha fluorescent proteins
    Rhonda E Wooten
    Department of Internal Medicine, Section on Infectious Diseases, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Biochim Biophys Acta 1783:1544-50. 2008
    ..We propose that AA is a signal for Ca2+-independent cPLA2alpha translocation and that lipid bodies are common targets of cPLA2alpha and contributors to stimulus-induced lipid mediator synthesis...
  45. pmc Apoptosis induced by ozone and oxysterols in human alveolar epithelial cells
    Beata Kosmider
    Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    Free Radic Biol Med 48:1513-24. 2010
    ..Understanding the response of human ATI-like cells and ATII cells to oxysterols may be useful for further studies, because these compounds may represent useful biomarkers in other diseases...
  46. pmc Low-concentration ozone reacts with plasmalogen glycerophosphoethanolamine lipids in lung surfactant
    Kelly M Wynalda
    Department of Pharmacology, University of Colorado Denver, MS 8303, 12801 E 17th Ave, Aurora, Colorado 80045, USA
    Chem Res Toxicol 23:108-17. 2010
    ..Lysophospholipids, pentadecanal, and nonanal were found to be the primary products of surfactant ozone oxidation...
  47. pmc Effects of acrolein on leukotriene biosynthesis in human neutrophils
    Karin A Zemski Berry
    Department of Pharmacology, MSC 8303, University of Colorado Denver, RC1 South, L18 6120, 12801 East 17th Avenue, P O Box 6511, Aurora, Colorado 80045, USA
    Chem Res Toxicol 21:2424-32. 2008
    ....
  48. pmc Cytosolic phospholipase a2 activation by Candida albicans in alveolar macrophages: role of dectin-1
    Rajinder P Parti
    Department of Pediatrics, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
    Am J Respir Cell Mol Biol 42:415-23. 2010
    ..The results demonstrate that dectin-1 mediates the acute activation of cPLA(2)alpha in GM-CSF-primed alveolar macrophages, but not in the more delayed phase of AA release and GM-CSF-dependent prostanoid production...
  49. pmc Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: human F-actin and DNA as targets for therapy
    Quinn M Parks
    Department of Medicine, National Jewish Health, 1400 Jackson, Denver, CO, USA
    J Med Microbiol 58:492-502. 2009
    ..aeruginosa. Neutrophil F-actin represents a potential new therapeutic target for disruption of pathogenic biofilms...
  50. pmc Role of phosphorylation and basic residues in the catalytic domain of cytosolic phospholipase A2alpha in regulating interfacial kinetics and binding and cellular function
    Dawn E Tucker
    Program in Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA
    J Biol Chem 284:9596-611. 2009
    ..The results demonstrate that Ser-505 phosphorylation and basic residues in the catalytic domain principally act to regulate cPLA(2)alpha hydrolytic activity...
  51. pmc Expression of phospholipases A2 in primary human lung macrophages: role of cytosolic phospholipase A2-alpha in arachidonic acid release and platelet activating factor synthesis
    Giorgio Giannattasio
    Department of Clinical Immunology and Allergy and Center for Basic and Clinical Immunology Research CISI, University of Naples Federico II, Via S Pansini 5, 80131 Naples, Italy
    Biochim Biophys Acta 1791:92-102. 2009
    ..Our results indicate that human macrophages express cPLA(2)-alpha, iPLA(2) and several sPLA(2)s. Cytosolic PLA(2)-alpha is the major enzyme responsible for lipid mediator production in human macrophages...
  52. pmc Impaired apoptotic cell clearance in CGD due to altered macrophage programming is reversed by phosphatidylserine-dependent production of IL-4
    Ruby F Fernandez-Boyanapalli
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Blood 113:2047-55. 2009
    ....
  53. pmc NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A
    S Courtney Frasch
    Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA
    J Biol Chem 283:33736-49. 2008
    ....
  54. pmc Transcriptional and translational regulation of TGF-beta production in response to apoptotic cells
    Yi Qun Xiao
    Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 181:3575-85. 2008
    ..Strikingly, these induction pathways for TGF-beta production were different from those initiated in the same cells responding to LPS or PMA...
  55. pmc Regulation of cytosolic phospholipase A2alpha by hsp90 and a p54 kinase in okadaic acid-stimulated macrophages
    Dawn E Tucker
    Program in Cell Biology, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206, USA
    J Leukoc Biol 84:798-806. 2008
    ..The results demonstrate a role for hsp90 in regulating cPLA(2)alpha-mediated AA release that involves association of a p54 kinase with cPLA(2)alpha upon OA stimulation...
  56. pmc Specific translocation of protein kinase Calpha to the plasma membrane requires both Ca2+ and PIP2 recognition by its C2 domain
    John H Evans
    Molecular Biophysics Program and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, CO 80309 0215, USA
    Mol Biol Cell 17:56-66. 2006
    ..Instead, targeting specificity is provided by basic residues on beta-strands 3-4, which bind to plasma membrane PIP2...

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  2. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..