Host Defense Mechanisms in Chronic Lung Disease

Summary

Principal Investigator: JO RAE R WRIGHT
Affiliation: Duke University Medical Center
Country: USA
Abstract: The overall goal of this SCCOR proposal is to elucidate the roles of innate and adaptive immunity in the pathogenesis of chronic lung disease. The SCCOR proposal consists of four interrelated research projects that are focused on two chronic lung diseases: asthma and bronchiolitis obliterans syndrome (BOS) with a common underlying theme of epithelial injury, inflammation, repair and fibroproliferation. The central hypothesis to be tested is that chronic lung disease occurs as a consequence of destructive or maladaptive host responses to common environmental insults that challenge the lung. The fundamental roles of innate and adaptive host responses are to recognize invading antigens, pathogens or altered self components with the purpose of eradicating the offending agents and restoring tissue integrity. While resolution can occur when the host response is normal, an exogenous insult cannot be contained when a critical host factor is inactivated, dysregulated, or becomes dysfunctional. Such maladaptive host responses lead to chronic lung disease. The project specific hypotheses within this SCCOR proposal are: Project 1: Surfactant proteins SP-A and SP-D, which are produced by both alveolar and airway cells, interact with cells of both the adaptive and innate immune systems to coordinately maximize defense against inhaled allergens and that cause and exacerbate asthma, while minimizing an over exuberant immune response that could result in inflammation, tissue damage and chronic lung disease. Project 2: Interleukin 13 (IL-13) modulates airway fibroblast function in human asthma via increased expression of platelet-derived growth factor (PDGF), an adaptive host response, and subsequent airway remodeling via fibroblast proliferation, collagen expression and decreased elastin expression. Project 3: Activation of innate immunity through toll like receptors (TLRs) in the transplanted lung promotes the adaptive alloimmune response leading to acute rejection and BOS. Project 4: Innate immune mechanisms regulate chronic inflammation and tissue remodeling and specifically, host hyaluronan and TLR interactions are critical components of the injury and repair response in non-infectious lung injury, BOS and chronic asthma. These studies will contribute to our understanding of normal and altered host responses on lung structure and function and will provide a basis for investigation and development of new therapies for the treatment of chronic lung diseases. (End of Abstract) INDIVIDUAL PROJECTS AND CORE UNITS PROJECT 1. Immunoprotective Effects of Surfactant Proteins in Asthma (Wright, Jo R.) Although pulmonary surfactant has been traditionally viewed as a surface tension reducing substance, recent studies demonstrate that it also functions in host defense. Two surfactant proteins, SP-A and SP-D, are members of a family of innate immune proteins known as collectins that bind pathogens and facilitate their clearance by immune cells. SP-A and SP-D also regulate a variety of immune cell functions. The overall hypothesis to be tested in this proposal is that SP-A and SP-D. which are synthesized and secreted by both alveolar and airway cells, interact with cells of both the adaptive and innate immune systems to coordinatelv maximize defense against inhaled allergens that cause and exacerbate asthma, while minimizing an over exuberant immune response that could result in persistent inflammation, tissue damage and chronic lung disease. We propose to evaluate the roles of SP-A and SP-D in regulating functions of two immune cells that play a role in asthma pathogenesis: dendritic cells and T-lymphocytes. Preliminary studies show that SP-D enhances antigen uptake and presentation by dendritic cells, that SP-A and SP-D inhibit lymphocyte proliferation, modulate production of regulatory and inflammatory cvtokines by dendritic cells and that SP-A null mice have enhanced susceptibility to lung injury and allergic inflammation. Our hypothesis is also supported by published studies showing that SP-A and SP-D inhibit allergen-induced lymphocyte proliferation and histamine release by immune cells from asthmatic children and by studies showing that SP-D null mice are more susceptible to allergic inflammation. Four aims are proposed. Aim 1 will determine the mechanisms by which SP-A and SP-D and their receptors, including toll like receptors (TLRs), regulate dendritic cell function. Studies will be conducted in vitro with isolated cells and in vivo with mice. Aim 2 will investigate the mechanism by which SP-A and SP-D regulate lymphocyte activation and whether SP-A and SP-D directly or indirectly (via dendritic cells) affect T-cell proliferation and polarization to a TH1 or Tn2 phenotype. Aim 3 is to investigate the role of SP-A and SP-D in the pathogenesis of inflammatory lung disease using mouse models of asthma and chronic allergic inflammation in collectin null mice. Aim 4 is to compare characterize levels of SP-A and SP-D in lavage fluid from asthmatics and normals. These studies will provide information about the role of SP-A and SP-D in regulating the functions of two important cells of the adaptive immune system and contribute to our understanding of the role of SPA and SP-D inflammatory lung diseases. This project investigates the role of TLRs in chronic lung disease in conjunction with Projects 2, 3 and 4. In addition, patient samples from Project 2 will be analyzed. The project will interact with all the Cores. (End of Abstract)
Funding Period: 2006-09-19 - 2011-07-31
more information: NIH RePORT

Top Publications

  1. pmc Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients
    Laurie D Snyder
    Department of Medicine, Duke University, Durham, NC 27710, USA
    Chest 144:226-33. 2013
  2. pmc Obesity, metabolic dysregulation and oxidative stress in asthma
    Njira L Lugogo
    Department of Medicine, Duke University, Durham, NC, USA
    Biochim Biophys Acta 1810:1120-6. 2011
  3. pmc Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype
    Njira L Lugogo
    Duke University Medical Center, P O Box 2629, Durham, NC 27710, USA
    Am J Respir Crit Care Med 186:404-11. 2012
  4. pmc Pulmonary fibrosis: patterns and perpetrators
    Paul W Noble
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
    J Clin Invest 122:2756-62. 2012
  5. pmc Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation
    F L Kelly
    Division of Pulmonary and Critical Care Medicine Duke University Medical Center, Durham, North Carolina, USA
    Am J Transplant 12:3076-84. 2012
  6. pmc Role of hyaluronan and hyaluronan-binding proteins in human asthma
    Jiurong Liang
    Division of Pulmonary, Allergy and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA
    J Allergy Clin Immunol 128:403-411.e3. 2011
  7. pmc Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44
    Yuejuan Li
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
    J Exp Med 208:1459-71. 2011
  8. pmc Surfactant protein A is defective in abrogating inflammation in asthma
    Ying Wang
    Department of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Physiol Lung Cell Mol Physiol 301:L598-606. 2011
  9. pmc The state of genome-wide association studies in pulmonary disease: a new perspective
    Jamie L Todd
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Am J Respir Crit Care Med 184:873-80. 2011
  10. pmc Acute allograft rejection: cellular and humoral processes
    Tereza Martinu
    Lung and Heart Lung Transplant Program, Division of Pulmonary and Critical Care, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Clin Chest Med 32:295-310. 2011

Scientific Experts

  • David W Zaas
  • L D Snyder
  • T Martinu
  • C Ashley Finlen Copeland
  • J M Castor
  • Eric B Meltzer
  • Dianhua Jiang
  • PAUL WESLEY NOBLE
  • Loretta Que
  • Stavros Garantziotis
  • Jo Rae Wright
  • Amy M Pastva
  • Julie G Ledford
  • Sambuddho Mukherjee
  • Njira L Lugogo
  • Monica Kraft
  • Kymberly M Gowdy
  • Jiurong Liang
  • Charles Giamberardino
  • Scott M Palmer
  • Hisatsugu Goto
  • Kristi L Williams
  • Julia L Nugent
  • Ying Wang
  • Joseph M Thomas
  • W Michael Foster
  • S M Palmer
  • F L Kelly
  • W A Davis
  • Yoosun Jung
  • Maura Leonard
  • Jennifer L Ingram
  • Ting Xie
  • Bethany Hsia
  • Tony D Church
  • Christine V Kinnier
  • Jamie L Todd
  • Yuejuan Li
  • Bernice Lo
  • Dennis R Voelker
  • Hong Wei Chu
  • Simone Degan
  • Christopher A Lord
  • Joseph Thomas
  • John W Hollingsworth
  • Kathy Evans
  • B L Brockway
  • J A Martissa
  • N S Sindhwani
  • Dave Francisco
  • Erin Potts
  • Erin N Potts-Kant
  • Druhan L Howell
  • Ningshan Liu
  • Scott E Plevy
  • Michael Dee Gunn
  • Sin Ho Jung
  • J L Todd
  • V E Kennedy
  • R Jain
  • Diana M Cardona
  • E Pavlisko
  • B R Stripp
  • Sambudho Mukherjee
  • Kymberly Gowdy
  • J P Eu
  • Robert M Tighe
  • Riu Miura
  • Daniel Fertel
  • Yu Yamaguchi
  • Alice Gray
  • David B Goldstein
  • Francine L Kelly
  • Gregory D Sempowski
  • Lise Wogensen
  • Guirong Wang
  • Pitchaimani Kandasamy
  • Joanna Floros
  • Jason Christie
  • Dongliang Ge
  • Jennifer Ingram
  • Tony Church
  • Divya Bappanad
  • Michele M Kislan
  • Derek W Cain
  • Anne E Dixon
  • Katherine Evans
  • Kathryn Calame
  • William M Foster
  • George J Cianciolo

Detail Information

Publications40

  1. pmc Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients
    Laurie D Snyder
    Department of Medicine, Duke University, Durham, NC 27710, USA
    Chest 144:226-33. 2013
    ..While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes...
  2. pmc Obesity, metabolic dysregulation and oxidative stress in asthma
    Njira L Lugogo
    Department of Medicine, Duke University, Durham, NC, USA
    Biochim Biophys Acta 1810:1120-6. 2011
    ..Epidemiological data demonstrate an increased risk of developing incident asthma with increasing adiposity. While the vast majority of studies support the interaction between obesity and asthma, the causality is unclear...
  3. pmc Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype
    Njira L Lugogo
    Duke University Medical Center, P O Box 2629, Durham, NC 27710, USA
    Am J Respir Crit Care Med 186:404-11. 2012
    ..Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma...
  4. pmc Pulmonary fibrosis: patterns and perpetrators
    Paul W Noble
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
    J Clin Invest 122:2756-62. 2012
    ..Understanding the heterogeneity of these diseases and elucidating the final common pathways of fibrogenesis are critical for the development of efficacious therapies for severe fibrosing lung diseases...
  5. pmc Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation
    F L Kelly
    Division of Pulmonary and Critical Care Medicine Duke University Medical Center, Durham, North Carolina, USA
    Am J Transplant 12:3076-84. 2012
    ..Collectively, these complementary results illustrate that BOS involves a selective alteration in the distribution and function of bronchiolar Clara cells...
  6. pmc Role of hyaluronan and hyaluronan-binding proteins in human asthma
    Jiurong Liang
    Division of Pulmonary, Allergy and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA
    J Allergy Clin Immunol 128:403-411.e3. 2011
    ..Hyaluronan fragments stimulate macrophages to produce inflammatory cytokines. We hypothesized that hyaluronan and its receptors would play a role in human asthma...
  7. pmc Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44
    Yuejuan Li
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
    J Exp Med 208:1459-71. 2011
    ..Understanding the mechanisms leading to an invasive fibroblast phenotype could lead to novel approaches to the treatment of disorders characterized by severe tissue fibrosis...
  8. pmc Surfactant protein A is defective in abrogating inflammation in asthma
    Ying Wang
    Department of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Physiol Lung Cell Mol Physiol 301:L598-606. 2011
    ..pneumoniae infection compared with SP-A derived from normal subjects. We conclude that SP-A derived from asthmatic subjects does not abrogate inflammation effectively, and this dysfunction may be modulated by SP-A1/SP-A...
  9. pmc The state of genome-wide association studies in pulmonary disease: a new perspective
    Jamie L Todd
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Am J Respir Crit Care Med 184:873-80. 2011
    ....
  10. pmc Acute allograft rejection: cellular and humoral processes
    Tereza Martinu
    Lung and Heart Lung Transplant Program, Division of Pulmonary and Critical Care, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Clin Chest Med 32:295-310. 2011
    ..A greater understanding of the heterogeneous mechanisms of lung rejection is critical to developing effective therapies that target the precise pathophysiology of the disease and ultimately improve long-term lung transplant outcomes...
  11. pmc Protective role of T-bet and Th1 cytokines in pulmonary graft-versus-host disease and peribronchiolar fibrosis
    Kymberly M Gowdy
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
    Am J Respir Cell Mol Biol 46:249-56. 2012
    ..These results suggest that the interplay between local innate immunity and non-Th1 T cell subsets contribute to chronic pulmonary GVHD...
  12. pmc Bayesian probit regression model for the diagnosis of pulmonary fibrosis: proof-of-principle
    Eric B Meltzer
    Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA
    BMC Med Genomics 4:70. 2011
    ..The accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is a major clinical challenge. We developed a model to diagnose IPF by applying Bayesian probit regression (BPR) modelling to gene expression profiles of whole lung tissue...
  13. pmc Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation
    W A Davis
    Department of Medicine, Duke University, Durham, NC, USA
    Am J Transplant 12:745-52. 2012
    ..Further studies are needed to determine mechanisms of airflow impairment and whether aggressive clinical interventions could improve post-SSAR outcomes...
  14. pmc Long-term exposure of chemokine CXCL10 causes bronchiolitis-like inflammation
    Dianhua Jiang
    Division of Pulmonary, Duke University School of Medicine, 106 Research Drive, Durham, NC 27710, USA
    Am J Respir Cell Mol Biol 46:592-8. 2012
    ..The airway hyperplasia and T-cell inflammation were dependent on the presence of CXCR3. Therefore, long-term exposure of the chemokine CXCL10 in the lung causes bronchiolitis-like inflammation in mice...
  15. pmc Surfactant protein A integrates activation signal strength to differentially modulate T cell proliferation
    Sambuddho Mukherjee
    Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA
    J Immunol 188:957-67. 2012
    ..These effects are intrinsic to the global T cell population and are manifested in vivo in naive as well as memory phenotype T cells. Thus, SP-A appears to integrate signal thresholds to control T cell proliferation...
  16. pmc A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury
    Jiurong Liang
    Division of Pulmonary, Department of Medicine, Duke Univ School of Medicine, Durham, NC 27710, USA
    Am J Physiol Lung Cell Mol Physiol 302:L933-40. 2012
    ..Our data suggested a previously undiscovered role for MHCII IA/IE(int)CD11c(int) cells in apoptotic cell clearance and inflammation resolution...
  17. pmc Surfactant protein A modulates induction of regulatory T cells via TGF-β
    Sambuddho Mukherjee
    Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA
    J Immunol 188:4376-84. 2012
    ..Taken together, these findings support the hypothesis that SP-A affects T cell immune function by the induction of Tregs during activation...
  18. pmc Novel role for surfactant protein A in gastrointestinal graft-versus-host disease
    Kymberly M Gowdy
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 188:4897-905. 2012
    ..The results of these studies demonstrate that SP-A protects against the development of GI GVHD and establishes a role for SP-A in regulating the immune response in the GI tract...
  19. ncbi Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial
    C Ashley Finlen Copeland
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Heart Lung Transplant 30:990-6. 2011
    ..In the current analysis, we monitored a single-center subset of patients enrolled in the CMV prevention trial to determine if extended prophylaxis conferred a sustained long-term benefit and to assess its hematologic safety...
  20. pmc Innate immune activation potentiates alloimmune lung disease independent of chemokine (C-X-C motif) receptor 3
    Tereza Martinu
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Heart Lung Transplant 30:717-25. 2011
    ..We hypothesized that the chemokine (C-X-C motif) receptor 3 (CXCR3) receptor is necessary for the development of LPS-induced pulmonary GVHD...
  21. ncbi Toll-like receptors, innate immunity and lung transplantation
    Laurie D Snyder
    Department of Medicine, Duke University Medical Center, Box 103002, Durham, NC 27710, USA
    Front Biosci (Elite Ed) 1:600-4. 2009
    ..This report will review the current understanding of innate immunity in lung allograft rejection in both murine and human studies...
  22. pmc Does obesity produce a distinct asthma phenotype?
    Njira L Lugogo
    Department of Medicine, Duke University, Durham, North Carolina, USA
    J Appl Physiol (1985) 108:729-34. 2010
    ..Although the mechanisms underlying obesity in asthma require further investigation, obesity plays a major role in the asthma epidemic and likely results in a distinct phenotype of the disease...
  23. pmc Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation
    Laurie D Snyder
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Am J Respir Crit Care Med 181:1391-6. 2010
    ..More recently, in the era of routine prophylaxis and ganciclovir treatment, the adverse impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome has been challenged...
  24. pmc The role of surfactant protein A in bleomycin-induced acute lung injury
    Hisatsugu Goto
    Department of Cell Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Am J Respir Crit Care Med 181:1336-44. 2010
    ..SP-A levels are altered in the bronchoalveolar lavage (BAL) fluid and serum of patients with acute lung injury and acute respiratory distress syndrome, suggesting the importance of SP-A in the pathogenesis of acute lung injury...
  25. ncbi Acute cellular rejection and humoral sensitization in lung transplant recipients
    Tereza Martinu
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Semin Respir Crit Care Med 31:179-88. 2010
    ..Herein, we review the clinical presentation, diagnosis, mechanisms, and treatment of cellular and humoral rejection after lung transplantation...
  26. pmc Review: Collectins link innate and adaptive immunity in allergic airway disease
    Julie G Ledford
    Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Innate Immun 16:183-90. 2010
    ..Future studies are needed to elucidate whether alterations in SP-A and SP-D are a consequence and/or cause of allergic airway disease...
  27. pmc Gastroesophageal reflux and altered motility in lung transplant rejection
    J M Castor
    Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
    Neurogastroenterol Motil 22:841-50. 2010
    ..Although additional prospective studies are needed, fundoplication appears useful in the prevention or treatment of post-transplant BOS...
  28. pmc Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients
    C Ashley Finlen Copeland
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Respir Crit Care Med 182:784-9. 2010
    ..Despite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients...
  29. pmc Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation
    Amy M Pastva
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 186:2842-9. 2011
    ....
  30. pmc Hyaluronan as an immune regulator in human diseases
    Dianhua Jiang
    Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA
    Physiol Rev 91:221-64. 2011
    ..This review focuses on the role of hyaluronan as an immune regulator in human diseases...
  31. pmc Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis
    L D Snyder
    Department of Medicine Department of Surgery and Immunology Department of Biostatistics and Bioinformatics, Duke University, Durham, NC
    Am J Transplant 11:553-60. 2011
    ..Thus, valganciclovir prophylaxis does not appear to impair the development of CMV-specific immunity in lung transplantation...
  32. pmc Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant
    Christine V Kinnier
    Department of Medicine, Duke University Medical Center, 106 Research Drive, Building MSRB2 Room 2100B, Durham, NC 27710, USA
    Transpl Immunol 24:83-93. 2011
    ....
  33. pmc Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation through regulation of HMGB-1 cytokine activity
    Julie G Ledford
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 185:3884-94. 2010
    ..pneumoniae-induced DC maturation by regulating HMGB-1 cytokine activity...
  34. pmc SP-A preserves airway homeostasis during Mycoplasma pneumoniae infection in mice
    Julie G Ledford
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 182:7818-27. 2009
    ..Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-alpha response...
  35. pmc S-nitrosoglutathione reductase: an important regulator in human asthma
    Loretta G Que
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    Am J Respir Crit Care Med 180:226-31. 2009
    ..Recently we showed that S-nitrosoglutathione reductase (GSNOR) regulates endogenous SNOs. Mice with genetic deletion of GSNOR are protected from airway hyperresponsivity in an allergic asthma model...
  36. pmc Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1
    Christopher A Lord
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 182:2948-58. 2009
    ..Analysis of Blimp-1(-/-) murine myeloid cells provides physiologic evidence that Blimp-1 reduces NLRP12 gene expression during cell differentiation. This demonstrates a novel role for Blimp-1 in the regulation of an NLR gene...
  37. pmc Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa
    David W Zaas
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:9955-64. 2009
    ..The success of Pseudomonas in co-opting lipid raft-mediated endocytosis to invade lung epithelial cells may depend on the relative strengths of these counteracting signaling activities...
  38. ncbi Alloimmune lung injury induced by local innate immune activation through inhaled lipopolysaccharide
    Stavros Garantziotis
    Department of Medicine, Duke University Medical Center, Durham, NC 27709, USA
    Transplantation 84:1012-9. 2007
    ..We have developed and pursued the hypothesis that local activation of pulmonary innate immunity through toll-like receptor (TLR)-4 is critical to the development of posttransplant alloimmune lung injury...
  39. pmc Immunomodulatory roles of surfactant proteins A and D: implications in lung disease
    Amy M Pastva
    Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, NC 27710, USA
    Proc Am Thorac Soc 4:252-7. 2007
    ..Numerous polymorphisms of SPs have been identified that may potentially possess differential functional abilities and may act via different receptors to ultimately alter the susceptibility to or severity of lung diseases...