Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation

Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation impairment. The syndrome is most commonly a manifestation of sepsis-induced organ dysfunction, characterized by disruption of endothelial barrier integrity and diffuse lung damage. Imbalance between coagulation and inflammation is a predominant characteristic of ARDS, leading to extreme inflammatory response and diffuse fibrin deposition in vascular capillary bed and alveoli. Activated platelets, neutrophils, endothelial cells, neutrophil extracellular traps, microparticles, and coagulation proteases, participate in the complex process of immunothrombosis, which is a key event in ARDS pathophysiology. The present review is focused on the elucidation of immunothrombosis in ARDS and the potential therapeutic implications.

[1]  D. Talmor,et al.  Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial. , 2016, JAMA.

[2]  I. Papassotiriou,et al.  Thrombocytopenia in critically ill patients with severe sepsis/septic shock: Prognostic value and association with a distinct serum cytokine profile. , 2016, Journal of critical care.

[3]  J. Wetterslev,et al.  Antithrombin III for critically ill patients. , 2016, The Cochrane database of systematic reviews.

[4]  D. Kor,et al.  Platelets in the pathogenesis of acute respiratory distress syndrome. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[5]  B. Griffith,et al.  Preoperative Aspirin Use and Lung Injury After Aortic Valve Replacement Surgery: A Retrospective Cohort Study , 2015, Anesthesia and analgesia.

[6]  R. Castillo,et al.  Transfusion-Related Acute Lung Injured (TRALI): Current Concepts , 2015, The open respiratory medicine journal.

[7]  A. Medford,et al.  Advances in Understanding of the Pathogenesis of Acute Respiratory Distress Syndrome , 2015, Respiration.

[8]  G. Bernard,et al.  Prehospital Aspirin Use Is Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Patients: A Propensity-Adjusted Analysis* , 2015, Critical care medicine.

[9]  D. McAuley,et al.  Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis , 2015, Critical Care.

[10]  H. Haugaa,et al.  Molecular adsorbent recirculating system treatment in 69 patients listed for liver transplantation , 2015, Critical Care.

[11]  Y. Otomo,et al.  Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock , 2015, Critical Care.

[12]  A. Kurosaki,et al.  Recombinant Human Soluble Thrombomodulin Treatment for Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Retrospective Study , 2015, Respiration.

[13]  J. Laffey,et al.  Mesenchymal stromal cell therapies: potential and pitfalls for ARDS. , 2015, Minerva anestesiologica.

[14]  R. Mallampalli,et al.  The Acute Respiratory Distress Syndrome: From Mechanism to Translation , 2015, The Journal of Immunology.

[15]  J. Higaki,et al.  Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients , 2014, Drug design, development and therapy.

[16]  P. Ward,et al.  Critical Role for the NLRP3 Inflammasome during Acute Lung Injury , 2014, The Journal of Immunology.

[17]  Bernd Engelmann,et al.  Biological basis and pathological relevance of microvascular thrombosis. , 2014, Thrombosis research.

[18]  T. van der Poll,et al.  The coagulation system and its function in early immune defense , 2014, Thrombosis and Haemostasis.

[19]  Wan-dong Liang,et al.  Protectin D1 promotes resolution of inflammation in a murine model of lipopolysaccharide‐induced acute lung injury via enhancing neutrophil apoptosis , 2014, Chinese medical journal.

[20]  H. Hemker,et al.  Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. , 2014, Blood.

[21]  Charles N Serhan,et al.  Resolution of acute inflammation in the lung. , 2014, Annual review of physiology.

[22]  R. Chambers,et al.  The mercurial nature of neutrophils: still an enigma in ARDS? , 2014, American journal of physiology. Lung cellular and molecular physiology.

[23]  D. Prough,et al.  Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome , 2014, The journal of trauma and acute care surgery.

[24]  A. Oxenius,et al.  TREM-1 Deficiency Can Attenuate Disease Severity without Affecting Pathogen Clearance , 2014, PLoS pathogens.

[25]  S. Zanotti,et al.  Severe sepsis and septic shock , 2013, Virulence.

[26]  K. Ataga,et al.  Hemostatic abnormalities in sickle cell disease , 2013, Current opinion in hematology.

[27]  M. Rapała-Kozik,et al.  Neutrophil extracellular traps (NETs) - formation and implications. , 2013, Acta biochimica Polonica.

[28]  Mark Roest,et al.  High Precision Platelet Releasate Definition by Quantitative Reversed Protein Profiling—Brief Report , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[29]  C. Smith,et al.  Histone induced platelet aggregation is inhibited by normal albumin. , 2013, Thrombosis research.

[30]  R. Casaburi,et al.  A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. , 2013, Chest.

[31]  Mingyao Li,et al.  IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL-1 receptor antagonist. , 2013, American journal of respiratory and critical care medicine.

[32]  L. Otterbein,et al.  Mitochondrial DAMPs Increase Endothelial Permeability through Neutrophil Dependent and Independent Pathways , 2013, PloS one.

[33]  P. Kubes,et al.  Neutrophil recruitment and function in health and inflammation , 2013, Nature Reviews Immunology.

[34]  I. Mitroulis,et al.  The emerging role of neutrophils in thrombosis—the journey of TF through NETs , 2012, Front. Immun..

[35]  B. Engelmann,et al.  Thrombosis as an intravascular effector of innate immunity , 2012, Nature Reviews Immunology.

[36]  S. Gill,et al.  Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury. , 2012, American journal of respiratory cell and molecular biology.

[37]  A. Girod,et al.  Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracellular Traps in Human Sepsis , 2012, PloS one.

[38]  M. Radic,et al.  Neutrophil Extracellular Traps: Double-Edged Swords of Innate Immunity , 2012, The Journal of Immunology.

[39]  D. Talmor,et al.  Lung Injury Prevention with Aspirin (LIPS-A): a protocol for a multicentre randomised clinical trial in medical patients at high risk of acute lung injury , 2012, BMJ Open.

[40]  W. Kuebler,et al.  Microparticles and acute lung injury. , 2012, American journal of physiology. Lung cellular and molecular physiology.

[41]  D. Wagner,et al.  Neutrophil extracellular trap (NET) impact on deep vein thrombosis. , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[42]  Z. Werb,et al.  Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. , 2012, The Journal of clinical investigation.

[43]  S. Ryter,et al.  Inflammasome-regulated cytokines are critical mediators of acute lung injury. , 2012, American journal of respiratory and critical care medicine.

[44]  M. Levi,et al.  Bronchoalveolar Activation of Coagulation and Inhibition of Fibrinolysis during Ventilator-Associated Lung Injury , 2012, Critical care research and practice.

[45]  D. Rowlands,et al.  Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury , 2012, Nature Medicine.

[46]  A. Walch,et al.  Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo , 2012, The Journal of experimental medicine.

[47]  K. Preissner,et al.  Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. , 2012, American journal of respiratory and critical care medicine.

[48]  K. Preissner,et al.  Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones , 2012, PloS one.

[49]  Ying-wei Wang,et al.  Altered proteomic pattern in platelets of rats with sepsis. , 2012, Blood cells, molecules & diseases.

[50]  J. Laffey,et al.  Mesenchymal stem cells - a promising therapy for Acute Respiratory Distress Syndrome , 2012, F1000 medicine reports.

[51]  D. Wagner,et al.  Neutrophil extracellular traps promote deep vein thrombosis in mice , 2012, Journal of thrombosis and haemostasis : JTH.

[52]  S. Negrotto,et al.  Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets , 2011, Thrombosis and Haemostasis.

[53]  J. Hartwig,et al.  Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. , 2011, Blood.

[54]  Robert A. Campbell,et al.  Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation , 2011, PLoS pathogens.

[55]  D. Talmor,et al.  Association of prehospitalization aspirin therapy and acute lung injury: Results of a multicenter international observational study of at-risk patients* , 2011, Critical care medicine.

[56]  W. Ruf,et al.  Protease-activated receptor 2 signaling in inflammation , 2011, Seminars in Immunopathology.

[57]  S. Adachi,et al.  Singlet oxygen is essential for neutrophil extracellular trap formation. , 2011, Biochemical and biophysical research communications.

[58]  J. Bastarache,et al.  Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome. , 2011, Current pharmaceutical biotechnology.

[59]  N. Palaniyar,et al.  Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping , 2011, The Journal of Immunology.

[60]  G. Bernard,et al.  Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome* , 2011, Critical care medicine.

[61]  N. Mackman,et al.  Microparticles in Hemostasis and Thrombosis , 2011, Circulation research.

[62]  D. Gibbons,et al.  Clinical trials for stem cell therapies , 2011, BMC medicine.

[63]  G. Camussi,et al.  Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[64]  T. McIntyre,et al.  Lipopolysaccharide Signaling without a Nucleus: Kinase Cascades Stimulate Platelet Shedding of Proinflammatory IL-1β–Rich Microparticles , 2011, The Journal of Immunology.

[65]  W. Jy,et al.  Microparticles in stored red blood cells as potential mediators of transfusion complications , 2011, Transfusion.

[66]  B. Binder,et al.  Efficient phagocytosis of periodontopathogens by neutrophils requires plasma factors, platelets and TLR2 , 2011, Journal of thrombosis and haemostasis : JTH.

[67]  M. Uchiba [Activated protein C]. , 2011, Rinsho byori. The Japanese journal of clinical pathology.

[68]  L. Papazian,et al.  High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome , 2011, Critical care.

[69]  J. Freyssinet,et al.  Cellular Mechanisms Underlying the Formation of Circulating Microparticles , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[70]  C. Weber,et al.  Microparticles: Protagonists of a Novel Communication Network for Intercellular Information Exchange , 2010, Circulation research.

[71]  B. Dixon,et al.  Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury , 2010, Critical care.

[72]  Bill B. Chen,et al.  Dynamic regulation of cardiolipin by the lipid pump, ATP8b1, determines the severity of lung injury in experimental bacterial pneumonia , 2010, Nature Medicine.

[73]  A. Loundou,et al.  Neuromuscular blockers in early acute respiratory distress syndrome. , 2010, The New England journal of medicine.

[74]  W. Ruf New players in the sepsis-protective activated protein C pathway. , 2010, The Journal of clinical investigation.

[75]  T. van der Poll,et al.  Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury. , 2010, Journal of aerosol medicine and pulmonary drug delivery.

[76]  H. Chou,et al.  Effects of Activated Protein C on Ventilator-Induced Lung Injury in Rats , 2010, Respiration.

[77]  W. Junger,et al.  Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury , 2009, Nature.

[78]  M. Matthay,et al.  Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. , 2009, The Journal of clinical investigation.

[79]  Jun Xu,et al.  Extracellular histones are major mediators of death in sepsis , 2009, Nature Medicine.

[80]  J. Bastarache,et al.  Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[81]  C. Serhan,et al.  15-epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. , 2009, American journal of respiratory and critical care medicine.

[82]  M. Asaduzzaman,et al.  Platelets support pulmonary recruitment of neutrophils in abdominal sepsis* , 2009, Critical care medicine.

[83]  E. Hoffman,et al.  Sepsis alters the megakaryocyte-platelet transcriptional axis resulting in granzyme B-mediated lymphotoxicity. , 2009, American journal of respiratory and critical care medicine.

[84]  J. Freyssinet,et al.  Microparticles in endothelial cell and vascular homeostasis: are they really noxious? , 2009, Haematologica.

[85]  Andrew C. Miller,et al.  Influence of Nebulized Unfractionated Heparin and N-Acetylcysteine in Acute Lung Injury After Smoke Inhalation Injury , 2009, Journal of burn care & research : official publication of the American Burn Association.

[86]  H. Herwald,et al.  Activation of the Human Contact System on Neutrophil Extracellular Traps , 2009, Journal of Innate Immunity.

[87]  L. DelGiudice,et al.  The role of tissue factor and tissue factor pathway inhibitor in health and disease states. , 2009, Journal of veterinary emergency and critical care.

[88]  Arthur S Slutsky,et al.  Ventilator-induced coagulopathy in experimental Streptococcus pneumoniae pneumonia , 2008, European Respiratory Journal.

[89]  I. Ott,et al.  Modulation of tissue factor and tissue factor pathway inhibitor-1 by neutrophil proteases , 2008, Thrombosis and Haemostasis.

[90]  M. Siegel,et al.  Randomized clinical trial of activated protein C for the treatment of acute lung injury. , 2008, American journal of respiratory and critical care medicine.

[91]  J. Catravas,et al.  Endothelial pathomechanisms in acute lung injury , 2008, Vascular Pharmacology.

[92]  M. Hollenberg,et al.  Role of protease‐activated receptors in inflammatory responses, innate and adaptive immunity , 2008, Journal of leukocyte biology.

[93]  M. Matthay,et al.  Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[94]  B. Brenner,et al.  Tissue factor and cancer. , 2008, Seminars in thrombosis and hemostasis.

[95]  K. Preissner,et al.  Current view on alveolar coagulation and fibrinolysis in acute inflammatory and chronic interstitial lung diseases , 2008, Thrombosis and Haemostasis.

[96]  C. Derian,et al.  'Role reversal' for the receptor PAR1 in sepsis-induced vascular damage , 2007, Nature Immunology.

[97]  Volker Brinkmann,et al.  Beneficial suicide: why neutrophils die to make NETs , 2007, Nature Reviews Microbiology.

[98]  T. Geiser,et al.  The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor , 2007, Thorax.

[99]  K. Ley,et al.  Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. , 2006, The Journal of clinical investigation.

[100]  T. van der Poll,et al.  Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury , 2006, Anesthesiology.

[101]  C. Roussos,et al.  Inhaled activated protein C attenuates lung injury induced by aerosolized endotoxin in mice. , 2006, Vascular pharmacology.

[102]  P. Parsons,et al.  Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome* , 2006, Critical care medicine.

[103]  A. Zychlinsky,et al.  Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms , 2006, Cellular microbiology.

[104]  T. van der Poll,et al.  Tissue factor in infection and severe inflammation. , 2006, Seminars in thrombosis and hemostasis.

[105]  S. Moochhala,et al.  Chemokines in acute respiratory distress syndrome , 2005, American journal of physiology. Lung cellular and molecular physiology.

[106]  M. Astiz,et al.  Importance of platelets and fibrinogen in neutrophil-endothelial cell interactions in septic shock , 2004, Critical care medicine.

[107]  G. Escolar,et al.  Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. , 2004, Blood.

[108]  S. Dudek,et al.  Pulmonary Endothelial Cell Barrier Enhancement by Sphingosine 1-Phosphate , 2004, Journal of Biological Chemistry.

[109]  T. van der Poll,et al.  Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia , 2004, Thorax.

[110]  M. Matthay,et al.  Protein C and thrombomodulin in human acute lung injury. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[111]  C. Sprung,et al.  Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. , 2003, JAMA.

[112]  N. Petasis,et al.  Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. , 2002, Journal of the American Society of Nephrology : JASN.

[113]  Patrick André,et al.  Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. , 2002, Circulation.

[114]  J. Vincent,et al.  Platelet function in sepsis , 2002, Journal of thrombosis and haemostasis : JTH.

[115]  P. Thompson,et al.  Activation of Protease-Activated Receptor (PAR)-1, PAR-2, and PAR-4 Stimulates IL-6, IL-8, and Prostaglandin E2 Release from Human Respiratory Epithelial Cells1 , 2002, The Journal of Immunology.

[116]  M. Dubick,et al.  Effects of heparin and lisofylline on pulmonary function after smoke inhalation injury in an ovine model. , 2002, Critical care medicine.

[117]  F. Taylor Response of anticoagulant pathways in disseminated intravascular coagulation. , 2001, Seminars in thrombosis and hemostasis.

[118]  J Ean,et al.  Efficacy and safety of recombinant human activated protein C for severe sepsis. , 2001, The New England journal of medicine.

[119]  R. Heyderman,et al.  Circulating platelet–neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing , 1999, British journal of haematology.

[120]  A. C. MacCuish,et al.  Complications , 1999, Diabetic medicine : a journal of the British Diabetic Association.

[121]  R. Jordan,et al.  7E3 F(ab')2, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects against microangiopathic hemolytic anemia and microvascular thrombotic renal failure in baboons treated with C4b binding protein and a sublethal infusion of Escherichia coli. , 1997, Blood.

[122]  G. FitzGerald,et al.  Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. , 1997, The Journal of clinical investigation.

[123]  C. Serhan,et al.  Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[124]  T. Dahms,et al.  Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. , 1995, American journal of respiratory and critical care medicine.

[125]  K. Kolev,et al.  Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors. An in vitro cell culture model. , 1995, Stroke.

[126]  D. Hammer,et al.  Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. , 1992 .

[127]  A. Fein,et al.  Platelet-specific α-Granule Proteins and Thrombospondin in Bronchoalveolar Lavage in the Adult Respiratory Distress Syndrome , 1989 .

[128]  S. Vesconi,et al.  Pulmonary microthrombosis in severe adult respiratory distress syndrome. , 1988, Critical care medicine.

[129]  J. Rosing,et al.  Prothrombin activation on phospholipid membranes with positive electrostatic potential. , 1988, Biochemistry.

[130]  W. Zapol,et al.  Platelet function in acute respiratory failure , 1987, American journal of hematology.

[131]  W. Zapol,et al.  Pulmonary vascular obstruction in severe ARDS: angiographic alterations after i.v. fibrinolytic therapy. , 1987, AJR. American journal of roentgenology.

[132]  J. Tomashefski,et al.  The pulmonary vascular lesions of the adult respiratory distress syndrome. , 1983, The American journal of pathology.

[133]  W. Zapol,et al.  Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. , 1981, The American review of respiratory disease.

[134]  F. Grinnell,et al.  Fibroblast adhesion to fibrinogen and fibrin substrata: Requirement for cold-insoluble globulin (plasma fibronectin) , 1980, Cell.

[135]  R. Bone,et al.  Intravascular coagulation associated with the adult respiratory distress syndrome. , 1976, The American journal of medicine.

[136]  M. C. Martínez,et al.  Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells , 2017 .

[137]  O. Mynbaev,et al.  Intraoperative low-tidal-volume ventilation. , 2013, The New England journal of medicine.

[138]  Arthur S Slutsky,et al.  Acute Respiratory Distress Syndrome The Berlin Definition , 2012 .

[139]  M. Watkins Beyond Thrombosis: The Versatile Platelet in Critical Illness , 2011 .

[140]  J. Finigan,et al.  The coagulation system and pulmonary endothelial function in acute lung injury. , 2009, Microvascular research.

[141]  A. Weltermann,et al.  Circulating tissue factor-exposing microparticles. , 2008, Thrombosis research.

[142]  M. Hollenberg,et al.  Shpacovitch V, Feld M, Hollenberg MD et al.Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity. J Leukoc Biol 83:1309-1322 , 2008 .

[143]  Gary Garber,et al.  The efficacy and safety of recombinant human activated protein C for the treatment of patients with severe sepsis (vol 28, pg 48, 2000) , 2001 .

[144]  H. G. Boman,et al.  Peptide antibiotics and their role in innate immunity. , 1995, Annual review of immunology.

[145]  A. Fein,et al.  Platelet-specific alpha-granule proteins and thrombospondin in bronchoalveolar lavage in the adult respiratory distress syndrome. , 1989, Chest.

[146]  T. Saldeen,et al.  Intravascular coagulation in the lungs in experimental fat embolism. , 1969, Acta chirurgica Scandinavica.