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Semin Respir Crit Care Med 2004; 25(1): 85-93
DOI: 10.1055/s-2004-822308
Published by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Sepsis and the Lung Host Response

Charles W. Frevert1 , 2 , Thomas R. Martin1 , 2
  • 1Medical Research Service of the VA Puget Sound Medical Center, Seattle, Washington
  • 2Division of Pulmonary and Critical and Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington
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Publikationsverlauf

Publikationsdatum:
12. März 2004 (online)

    Lizenzen und Reprints

Sepsis is the leading cause of death in critically ill patients and is the most common risk factor for the development of acute lung injury in medical patients. Initially investigators hypothesized that an excessive proinflammatory response contributed to the pathogenesis of sepsis. However, this hypothesis overlooked the beneficial effects of proinflammatory mediators and the detrimental effects of an excessive anti-inflammatory response. This has led to a new hypothesis where sepsis is characterized by imbalances of the pro- and anti-inflammatory responses, with tissue injury the result of an excessive proinflammatory response and impaired pulmonary host defense the result of an excessive anti-inflammatory response. This article reviews clinical studies and animal models which show that sepsis results in an impaired lung host response to bacteria. Information in this article should provide the reader with an increased understanding of the pathogenesis of sepsis and the realization that new therapeutic strategies for sepsis need to take into account the need to balance pro- and anti-inflammatory responses to maintain pulmonary host defenses and prevent the development of acute lung injury.

KEYWORDS

Sepsis - innate immunity - pulmonary host defenses

REFERENCES

  • 1 Brun-Buisson C, Doyon F, Carlet J et al.. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults.  JAMA. 1995;  274 968-974
    CrossrefPubMedGoogle Scholar
  • 2 Angus D C, Linde-Zwirble W T, Lidicker J et al.. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.  Crit Care Med. 2001;  29 1303-1310
    CrossrefPubMedGoogle Scholar
  • 3 Pinner R W, Teutsch S M, Simonsen L et al.. Trends in infectious diseases mortality in the United States.  JAMA. 1996;  275 189-193
    CrossrefPubMedGoogle Scholar
  • 4 Simonsen L, Conn L A, Pinner R W, Teutsch S. Trends in infectious disease hospitalizations in the United States, 1980-1994.  Arch Intern Med. 1998;  158 1923-1928
    CrossrefPubMedGoogle Scholar
  • 5 McBean M, Rajamani S. Increasing rates of hospitalization due to septicemia in the US elderly population, 1986-1997.  J Infect Dis. 2001;  183 596-603
    CrossrefPubMedGoogle Scholar
  • 6 Bone R C, Balk R A, Cerra F B et al.. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee.  Chest. 1992;  101 1644-1655
    CrossrefPubMedGoogle Scholar
  • 7 Bone R C. Why sepsis trials fail.  JAMA. 1996;  276 565-566
    CrossrefPubMedGoogle Scholar
  • 8 Goldie A S, Fearon K C, Ross J A et al.. Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group.  JAMA. 1995;  274 172-177
    CrossrefPubMedGoogle Scholar
  • 9 Bone R C, Grodzin C J, Balk R A. Sepsis: a new hypothesis for pathogenesis of the disease process.  Chest. 1997;  112 235-243
    CrossrefPubMedGoogle Scholar
  • 10 Nelson S. A question of balance.  Am J Respir Crit Care Med. 1999;  159(5 Pt 1) 1365-1367
    PubMedGoogle Scholar
  • 11 Munford R S, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive.  Am J Respir Crit Care Med. 2001;  163 316-321
    CrossrefPubMedGoogle Scholar
  • 12 Hotchkiss R S, Karl I E. The pathophysiology and treatment of sepsis.  N Engl J Med. 2003;  348 138-150
    CrossrefPubMedGoogle Scholar
  • 13 Sibille Y, Reynolds H Y. Macrophages and polymorphonuclear neutrophils in lung defense and injury.  Am Rev Respir Dis. 1990;  141 471-501
    PubMedGoogle Scholar
  • 14 Standiford T J, Kunkel S L, Greenberger M J, Laichalk L L, Strieter R M. Expression and regulation of chemokines in bacterial pneumonia.  J Leukoc Biol. 1996;  59 24-28
    PubMedGoogle Scholar
  • 15 Zhang P, Summer W R, Bagby G J, Nelson S. Innate immunity and pulmonary host defense.  Immunol Rev. 2000;  173 39-51
    CrossrefPubMedGoogle Scholar
  • 16 Gordon S B, Read R C. Macrophage defences against respiratory tract infections.  Br Med Bull. 2002;  61 45-61
    CrossrefPubMedGoogle Scholar
  • 17 Hensler T, Hecker H, Heeg K et al.. Distinct mechanisms of immunosuppression as a consequence of major surgery.  Infect Immun. 1997;  65 2283-2291
    PubMedGoogle Scholar
  • 18 Hensler T, Heidecke C D, Hecker H et al.. Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production.  J Immunol. 1998;  161 2655-2659
    PubMedGoogle Scholar
  • 19 van der Poll T, de Wall Malefyt R, Coyle S M, Lowry S F. Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: sequential measurements of plasma soluble interleukin (IL)-1 receptor type II, IL-10, and IL-13.  J Infect Dis. 1997;  175 118-122
    PubMedGoogle Scholar
  • 20 Ferguson N R, Galley H F, Webster N R. T helper cell subset ratios in patients with severe sepsis.  Intensive Care Med. 1999;  25 106-109
    CrossrefPubMedGoogle Scholar
  • 21 Zimmer S, Pollard V, Marshall G D et al.. Effects of endotoxin on the Th1/Th2 response in humans.  J Burn Care Rehabil. 1996;  17(6 Pt 1) 491-496
    PubMedGoogle Scholar
  • 22 Lauw F N, ten Hove T, Dekkers P E et al.. Reduced Th1, but not Th2, cytokine production by lymphocytes after in vivo exposure of healthy subjects to endotoxin.  Infect Immun. 2000;  68 1014-1018
    CrossrefPubMedGoogle Scholar
  • 23 Olszyna D P, Pajkrt D, van Deventer S J, van der Poll T. Effect of interleukin 10 on the release of the CXC chemokines growth related oncogene GRO-alpha and epithelial cell-derived neutrophil activating peptide (ENA)-78 during human endotoxemia.  Immunol Lett. 2001;  78 41-44
    CrossrefPubMedGoogle Scholar
  • 24 Olszyna D P, Pajkrt D, Lauw F N, van Deventer S J, van Der Poll T. Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.  J Infect Dis. 2000;  181 613-620
    CrossrefPubMedGoogle Scholar
  • 25 Pajkrt D, Camoglio L, Buul T et al.. Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration.  J Immunol. 1997;  158 3971-3977
    PubMedGoogle Scholar
  • 26 Janeway Jr C A, Medzhitov R. Innate immune recognition.  Annu Rev Immunol. 2002;  20 197-216
    CrossrefPubMedGoogle Scholar
  • 27 Aderem A, Ulevitch R J. Toll-like receptors in the induction of the innate immune response.  Nature. 2000;  406 782-787
    CrossrefPubMedGoogle Scholar
  • 28 West M A, Heagy W. Endotoxin tolerance: a review.  Crit Care Med. 2002;  30(suppl 1) S64-S73
    PubMedGoogle Scholar
  • 29 Dobrovolskaia M A, Vogel S N. Toll receptors, CD14, and macrophage activation and deactivation by LPS.  Microbes Infect. 2002;  4 903-914
    CrossrefPubMedGoogle Scholar
  • 30 Munoz C, Carlet J, Fitting C et al.. Dysregulation of in vitro cytokine production by monocytes during sepsis.  J Clin Invest. 1991;  88 1747-1754
    PubMedGoogle Scholar
  • 31 Volk H D, Thieme M, Heym S et al.. Alterations in function and phenotype of monocytes from patients with septic disease: predictive value and new therapeutic strategies.  Behring Inst Mitt. 1991;  88 208-215
    PubMedGoogle Scholar
  • 32 Wilson C S, Seatter S C, Rodriguez J L et al.. In vivo endotoxin tolerance: impaired LPS-stimulated TNF release of monocytes from patients with sepsis, but not SIRS.  J Surg Res. 1997;  69 101-106
    CrossrefPubMedGoogle Scholar
  • 33 Docke W D, Randow F, Syrbe U et al.. Monocyte deactivation in septic patients: restoration by IFN-γ treatment.  Nat Med. 1997;  3 678-681
    CrossrefPubMedGoogle Scholar
  • 34 Wolk K, Docke W D, von Baehr V, Volk H D, Sabat R. Impaired antigen presentation by human monocytes during endotoxin tolerance.  Blood. 2000;  96 218-223
    PubMedGoogle Scholar
  • 35 Adib-Conquy M, Adrie C, Moine P et al.. NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance.  Am J Respir Crit Care Med. 2000;  162 1877-1883
    PubMedGoogle Scholar
  • 36 Sugawara S, Nemoto E, Tada H et al.. Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness.  J Immunol. 2000;  165 411-418
    PubMedGoogle Scholar
  • 37 Randow F, Syrbe U, Meisel C et al.. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta.  J Exp Med. 1995;  181 1887-1892
    CrossrefPubMedGoogle Scholar
  • 38 Park D R, Skerrett S J. IL-10 enhances the growth of Legionella pneumophila in human mononuclear phagocytes and reverses the protective effect of IFN-gamma: differential responses of blood monocytes and alveolar macrophages.  J Immunol. 1996;  157 2528-2538
    PubMedGoogle Scholar
  • 39 Raychaudhuri B, Fisher C J, Farver C F et al.. Interleukin 10 (IL-10)-mediated inhibition of inflammatory cytokine production by human alveolar macrophages.  Cytokine. 2000;  12 1348-1355
    CrossrefPubMedGoogle Scholar
  • 40 Cummings C J, Martin T R, Frevert C W et al.. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis.  J Immunol. 1999;  162 2341-2346
    PubMedGoogle Scholar
  • 41 Tavares-Murta B M, Zaparoli M, Ferreira R B et al.. Failure of neutrophil chemotactic function in septic patients.  Crit Care Med. 2002;  30 1056-1061
    PubMedGoogle Scholar
  • 42 Skoutelis A T, Kaleridis V, Athanassiou G M et al.. Neutrophil deformability in patients with sepsis, septic shock, and adult respiratory distress syndrome.  Crit Care Med. 2000;  28 2355-2359
    PubMedGoogle Scholar
  • 43 Schultz M J, Olszyna D P, de Jonge E et al.. Reduced ex vivo chemokine production by polymorphonuclear cells after in vivo exposure of normal humans to endotoxin.  J Infect Dis. 2000;  182 1264-1267
    CrossrefPubMedGoogle Scholar
  • 44 Ahmed N A, McGill S, Yee J et al.. Mechanisms for the diminished neutrophil exudation to secondary inflammatory sites in infected patients with a systemic inflammatory response (sepsis).  Crit Care Med. 1999;  27 2459-2468
    PubMedGoogle Scholar
  • 45 Laichalk L L, Danforth J M, Standiford T J. Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity.  FEMS Immunol Med Microbiol. 1996;  15 181-187
    PubMedGoogle Scholar
  • 46 Wright J R, Borron P, Brinker K G, Folz R J. Surfactant protein A: regulation of innate and adaptive immune responses in lung inflammation.  Am J Respir Cell Mol Biol. 2001;  24 513-517
    PubMedGoogle Scholar
  • 47 Korfhagen T R. Surfactant protein A (SP-A)-mediated bacterial clearance: SP-A and cystic fibrosis.  Am J Respir Cell Mol Biol. 2001;  25 668-672
    PubMedGoogle Scholar
  • 48 Crouch E, Wright J R. Surfactant proteins A and D and pulmonary host defense.  Annu Rev Physiol. 2001;  63 521-554
    CrossrefPubMedGoogle Scholar
  • 49 Tobias P S, Ulevitch R J. Lipopolysaccharide binding protein and CD14 in LPS dependent macrophage activation.  Immunobiology. 1993;  187 227-232
    PubMedGoogle Scholar
  • 50 Raymondos K, Leuwer M, Haslam P L et al.. Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis.  Crit Care Med. 1999;  27 82-89
    PubMedGoogle Scholar
  • 51 Greene K E, Wright J R, Steinberg K P et al.. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS.  Am J Respir Crit Care Med. 1999;  160 1843-1850
    CrossrefPubMedGoogle Scholar
  • 52 Cheng I W, Ware L B, Greene K E et al.. Prognostic value of surfactant proteins A and D in patients with acute lung injury.  Crit Care Med. 2003;  31 20-27
    PubMedGoogle Scholar
  • 53 Wurfel M M, Radella II F, Ruzinski J T et al.. Bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome facilitates bacterial lipopolysaccharide recognition: role for lipopolysaccharide-binding protein.  Am J Respir Crit Care Med. 2003;  167 A760
    PubMedGoogle Scholar
  • 54 Reddy R C, Chen G H, Tekchandani P K, Standiford T J. Sepsis-induced immunosuppression: from bad to worse.  Immunol Res. 2001;  24 273-287
    PubMedGoogle Scholar
  • 55 van der Poll T, Marchant A, Buurman W A et al.. Endogenous IL-10 protects mice from death during septic peritonitis.  J Immunol. 1995;  155 5397-5401
    PubMedGoogle Scholar
  • 56 van der Poll T, Jansen P M, Montegut W J et al.. Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia.  J Immunol. 1997;  158 1971-1975
    PubMedGoogle Scholar
  • 57 van der Poll T, Marchant A, Keogh C V, Goldman M, Lowry S F. Interleukin-10 impairs host defense in murine pneumococcal pneumonia.  J Infect Dis. 1996;  174 994-1000
    PubMedGoogle Scholar
  • 58 Greenberger M J, Strieter R M, Kunkel S L et al.. Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.  J Immunol. 1995;  155 722-729
    PubMedGoogle Scholar
  • 59 Steinhauser M L, Hogaboam C M, Kunkel S L et al.. IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense.  J Immunol. 1999;  162 392-399
    PubMedGoogle Scholar
  • 60 Reddy R C, Chen G H, Newstead M W et al.. Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10.  Infect Immun. 2001;  69 1394-1401
    CrossrefPubMedGoogle Scholar
  • 61 Kurahashi K, Kajikawa O, Sawa T et al.. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia.  J Clin Invest. 1999;  104 743-750
    CrossrefPubMedGoogle Scholar
  • 62 Sewnath M E, Olszyna D P, Birjmohun R et al.. IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance.  J Immunol. 2001;  166 6323-6331
    PubMedGoogle Scholar
  • 63 Hashimoto S, Pittet J F, Hong K et al.. Depletion of alveolar macrophages decreases neutrophil chemotaxis to Pseudomonas airspace infections.  Am J Physiol. 1996;  270 L819-L828
    PubMedGoogle Scholar
  • 64 Broug-Holub E, Toews G B, van Iwaarden J F et al.. Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival.  Infect Immun. 1997;  65 1139-1146
    PubMedGoogle Scholar
  • 65 Heagy W, Hansen W, Nieman K et al.. Impaired ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor production may identify “septic” intensive care unit patients.  Shock. 2000;  14 271-276; discussion 276-277
    PubMedGoogle Scholar
  • 66 Nomura F, Akashi S, Sakao Y et al.. Endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression.  J Immunol. 2000;  164 3476-3479
    PubMedGoogle Scholar
  • 67 Sato S, Nomura F, Kawai T et al.. Synergy and cross-tolerance between toll-like receptor (TLR) 2- and TLR-4-mediated signaling pathways.  J Immunol. 2000;  165 7096-7101
    PubMedGoogle Scholar
  • 68 Fahmi H, Chaby R. Desensitization of macrophages to endotoxin effects is not correlated with a down-regulation of lipopolysaccharide-binding sites.  Cell Immunol. 1993;  150 219-229
    CrossrefPubMedGoogle Scholar
  • 69 Jacinto R, Hartung T, McCall C, Li L. Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance: distinct alterations in il-1 receptor-associated kinase.  J Immunol. 2002;  168 6136-6141
    PubMedGoogle Scholar
  • 70 Shennib H, Chu-Jeng R, Mulder D, Richards G, Prentis J. Pulmonary bacterial clearance and alveolar macrophage function in septic shock lung.  Am Rev Respir Dis. 1984;  130 444-449
    PubMedGoogle Scholar
  • 71 Jacobs R F, Kiel D P, Balk R A. Alveolar macrophage function in a canine model of endotoxin-induced lung injury.  Am Rev Respir Dis. 1986;  134 745-751
    PubMedGoogle Scholar
  • 72 Jacobs R F, Dorsey D R, Tryka A F, Tabor D R. Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury.  Exp Lung Res. 1988;  14 359-374
    PubMedGoogle Scholar
  • 73 Tabor D, Kiel D, Jacobs R. Receptor-mediated ingestion responses by lung macrophages from a canine model of ARDS.  J Leukoc Biol. 1987;  41 539-543
    PubMedGoogle Scholar
  • 74 Mason C M, Dobard E, Summer W R, Nelson S. Intraportal lipopolysaccharide suppresses pulmonary antibacterial defense mechanisms.  J Infect Dis. 1997;  176 1293-1302
    PubMedGoogle Scholar
  • 75 Christman J W, Petras S F, Hacker M, Absher P M, Davis G S. Alveolar macrophage function is selectively altered after endotoxemia in rats.  Infect Immun. 1988;  56 1254-1259
    PubMedGoogle Scholar
  • 76 Frevert C W, Warner A E, Weller E, Brain J D. The effect of endotoxin on in vivo rat alveolar macrophage phagocytosis.  Exp Lung Res. 1998;  24 745-758
    PubMedGoogle Scholar
  • 77 Harris S E, Nelson S, Astry C L, Bainton B G, Summer W R. Endotoxin-induced suppression of pulmonary antibacterial defenses against Staphylococcus aureus.  Am Rev Respir Dis. 1988;  138 1439-1443
    PubMedGoogle Scholar
  • 78 Goya T, Abe M, Shimura H, Torisu M. Characteristics of alveolar macrophages in experimental septic lung.  J Leukoc Biol. 1992;  52 236-243
    PubMedGoogle Scholar
  • 79 Coffey M J, Phare S M, Peters-Golden M. Prolonged exposure to lipopolysaccharide inhibits macrophage 5-lipoxygenase metabolism via induction of nitric oxide synthesis.  J Immunol. 2000;  165 3592-3598
    PubMedGoogle Scholar
  • 80 Toews G B, Gross G N, Pierce A K. The relationship of inoculum size to lung bacterial clearance and phagocytic cell response in mice.  Am Rev Respir Dis. 1979;  120 559-566
    PubMedGoogle Scholar
  • 81 Rehm S R, Gross G N, Pierce A K. Early bacterial clearance from murine lungs. Species-dependent phagocyte response.  J Clin Invest. 1980;  66 194-199
    PubMedGoogle Scholar
  • 82 Onofrio J M, Toews G B, Lipscomb M F, Pierce A K. Granulocyte-alveolar-macrophage interaction in the pulmonary clearance of Staphylococcus aureus .  Am Rev Respir Dis. 1983;  127 335-341
    PubMedGoogle Scholar
  • 83 White J C, Nelson S, Winkelstien J, Booth F, Jakab G. Impairment of antibacterial defense mechanisms of the lung by extrapulmonary infection.  J Infect Dis. 1986;  153 202-208
    PubMedGoogle Scholar
  • 84 Nelson S, Chidiac C, Bagby G, Summer W R. Endotoxin-induced suppression of lung host defenses.  J Med. 1990;  21 85-103
    PubMedGoogle Scholar
  • 85 Nelson S, Mason C, Bagby G, Nakamura C, Summer W. Lipopolysaccharide-induced inhibition of intrapulmonary tumor necrosis factor and lung antibacterial defenses.  Am Rev Respir Dis. 1990;  141 A512
    PubMedGoogle Scholar
  • 86 Frevert C W, Warner A E, Kobzik L. Defective pulmonary recruitment of neutrophils in a rat model of endotoxemia.  Am J Respir Cell Mol Biol. 1994;  11 716-723
    PubMedGoogle Scholar
  • 87 Hirano S. Migratory responses of PMN after intraperitoneal and intratracheal administration of lipopolysaccharide.  Am J Physiol. 1996;  270(5 Pt 1) L836-L845
    PubMedGoogle Scholar
  • 88 Wagner J G, Harkema J R, Roth R A. Pulmonary leukostasis and the inhibition of airway neutrophil recruitment are early events in the endotoxemic rat.  Shock. 2002;  17 151-158
    PubMedGoogle Scholar
  • 89 Hartiala K T, Langlois L, Goldstein I M, Rosenbaum J T. Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors.  Infect Immun. 1985;  50 527-533
    PubMedGoogle Scholar
  • 90 Wagner J G, Driscoll K E, Roth R A. Inhibition of pulmonary neutrophil trafficking during endotoxemia is dependent on the stimulus for migration.  Am J Respir Cell Mol Biol. 1999;  20 769-776
    PubMedGoogle Scholar
  • 91 Bignold L P, Rogers S D, Siaw T M, Bahnisch J. Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria.  Infect Immun. 1991;  59 4255-4258
    PubMedGoogle Scholar
  • 92 Gimbrone Jr M A, Obin M S, Brock A F et al.. Endothelial interleukin-8: a novel inhibitor of leukocyte-endothelial interactions.  Science. 1989;  246 1601-1603
    PubMedGoogle Scholar
  • 93 Hechtman D H, Cybulsky M I, Fuchs H J, Baker J B, Gimbrone M J. Intravascular IL-8: inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation.  J Immunol. 1991;  147 883-892
    PubMedGoogle Scholar
  • 94 Sano H, Sata T, Nanri H, Ikeda M, Shigematsu A. Thioredoxin is associated with endotoxin tolerance in mice.  Crit Care Med. 2002;  30 190-194
    PubMedGoogle Scholar
  • 95 Nakamura H, Herzenberg L A, Bai J et al.. Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis.  Proc Natl Acad Sci USA. 2001;  98 15143-15148
    CrossrefPubMedGoogle Scholar
  • 96 Blackwell T S, Lancaster L H, Blackwell T R, Venkatakrishnan A, Christman J W. Chemotactic gradients predict neutrophilic alveolitis in endotoxin-treated rats.  Am J Respir Crit Care Med. 1999;  159 1644-1652
    PubMedGoogle Scholar
  • 97 Duffy A J, Nolan B, Sheth K et al.. Inhibition of alveolar neutrophil immigration in endotoxemia is macrophage inflammatory protein 2 independent.  J Surg Res. 2000;  90 51-57
    CrossrefPubMedGoogle Scholar
  • 98 Ferri L E, Swartz D, Christou N V. Soluble L-selectin at levels present in septic patients diminishes leukocyte-endothelial cell interactions in mice in vivo: a mechanism for decreased leukocyte delivery to remote sites in sepsis.  Crit Care Med. 2001;  29 117-122
    PubMedGoogle Scholar
  • 99 Benjamim C F, Ferreira S H, Cunha F Q. Role of nitric oxide in the failure of neutrophil migration in sepsis.  J Infect Dis. 2000;  182 214-223
    CrossrefPubMedGoogle Scholar
  • 100 Benjamim C F, Silva J S, Fortes Z B et al.. Inhibition of leukocyte rolling by nitric oxide during sepsis leads to reduced migration of active microbicidal neutrophils.  Infect Immun. 2002;  70 3602-3610
    CrossrefPubMedGoogle Scholar
  • 101 Crosara-Alberto D P, Darini A L, Inoue R Y et al.. Involvement of NO in the failure of neutrophil migration in sepsis induced by Staphylococcus aureus .  Br J Pharmacol. 2002;  136 645-658
    CrossrefPubMedGoogle Scholar
  • 102 Matute-Bello G, Frevert C W, Kajikawa O et al.. Septic shock and acute lung injury in rabbits with peritonitis. failure of the neutrophil response to localized infection.  Am J Respir Crit Care Med. 2001;  163 234-243
    PubMedGoogle Scholar
  • 103 Hotchkiss R S, Swanson P E, Freeman B D et al.. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction.  Crit Care Med. 1999;  27 1230-1251
    CrossrefPubMedGoogle Scholar
  • 104 Hotchkiss R S, Tinsley K W, Swanson P E et al.. Depletion of dendritic cells, but not macrophages, in patients with sepsis.  J Immunol. 2002;  168 2493-2500
    PubMedGoogle Scholar
  • 105 Hotchkiss R S, Tinsley K W, Swanson P E et al.. Prevention of lymphocyte cell death in sepsis improves survival in mice.  Proc Natl Acad Sci USA. 1999;  96 14541-14546
    CrossrefPubMedGoogle Scholar
  • 106 Hotchkiss R S, Chang K C, Swanson P E et al.. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte.  Nat Immunol. 2000;  1 496-501
    CrossrefPubMedGoogle Scholar
  • 107 Tinsley K W, Grayson M H, Swanson P E et al.. Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells.  J Immunol. 2003;  171 909-914
    PubMedGoogle Scholar
  • 108 Fadok V A, Bratton D L, Konowal A et al.. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.  J Clin Invest. 1998;  101 890-898
    CrossrefPubMedGoogle Scholar
  • 109 Fadok V A, Bratton D L, Henson P M. Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences.  J Clin Invest. 2001;  108 957-962
    CrossrefPubMedGoogle Scholar
  • 110 Fadok V A, Chimini G. The phagocytosis of apoptotic cells.  Semin Immunol. 2001;  13 365-372
    CrossrefPubMedGoogle Scholar
  • 111 Hotchkiss R S, Chang K C, Grayson M H et al.. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis.  Proc Natl Acad Sci USA. 2003;  100 6724-6729
    CrossrefPubMedGoogle Scholar
  • 112 Martin T R. Recognition of bacterial endotoxin in the lungs.  Am J Respir Cell Mol Biol. 2000;  23 128-132
    PubMedGoogle Scholar
  • 113 Fan M H, Klein R D, Steinstraesser L et al.. An essential role for lipopolysaccharide-binding protein in pulmonary innate immune responses.  Shock. 2002;  18 248-254
    PubMedGoogle Scholar
  • 114 Le Roy D, Di Padova F, Adachi Y et al.. Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria.  J Immunol. 2001;  167 2759-2765
    PubMedGoogle Scholar
  • 115 McCormack F X, Whitsett J A. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung.  J Clin Invest. 2002;  109 707-712
    CrossrefPubMedGoogle Scholar
  • 116 Sano H, Chiba H, Iwaki D et al.. Surfactant proteins A and D bind CD14 by different mechanisms.  J Biol Chem. 2000;  275 22442-22451
    CrossrefPubMedGoogle Scholar
  • 117 Guillot L, Balloy V, McCormack F X et al.. Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4.  J Immunol. 2002;  168 5989-5992
    CrossrefPubMedGoogle Scholar
  • 118 Wright J R. Immunomodulatory functions of surfactant.  Physiol Rev. 1997;  77 931-962
    PubMedGoogle Scholar
  • 119 Awasthi S, Coalson J J, Yoder B A, Crouch E, King R J. Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons.  Am J Respir Crit Care Med. 2001;  163 389-397
    PubMedGoogle Scholar
  • 120 LeVine A M, Kurak K E, Bruno M D et al.. Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection.  Am J Respir Cell Mol Biol. 1998;  19 700-708
    PubMedGoogle Scholar
  • 121 LeVine A M, Kurak K E, Wright J R et al.. Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice.  Am J Respir Cell Mol Biol. 1999;  20 279-286
    PubMedGoogle Scholar
  • 122 Chabot S, Salez L, McCormack F X, Touqui L, Chignard M. Surfactant protein A inhibits lipopolysaccharide-induced in vivo production of interleukin-10 by mononuclear phagocytes during lung inflammation.  Am J Respir Cell Mol Biol. 2003;  28 347-353
    CrossrefPubMedGoogle Scholar
  • 123 Abraham E. Neutrophils and acute lung injury.  Crit Care Med. 2003;  31(suppl 4) S195-199
    CrossrefPubMedGoogle Scholar
  • 124 LeVine A M, Whitsett J A, Gwozdz J A et al.. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung.  J Immunol. 2000;  165 3934-3940
    PubMedGoogle Scholar
  • 125 Bufler P, Schmidt B, Schikor D et al.. Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide.  Am J Respir Cell Mol Biol. 2003;  28 249-256
    CrossrefPubMedGoogle Scholar
  • 126 Augusto L A, Synguelakis M, Johansson J et al.. Interaction of pulmonary surfactant protein C with CD14 and lipopolysaccharide.  Infect Immun. 2003;  71 61-67
    CrossrefPubMedGoogle Scholar
  • 127 Augusto L A, Synguelakis M, Espinassous Q et al.. Cellular anti-endotoxin activities of lung surfactant protein C in lipid vesicles.  Am J Respir Crit Care Med. 2003;  168 335-341
    CrossrefPubMedGoogle Scholar
  • 128 Wang S C, Klein R D, Wahl W L et al.. Tissue coexpression of LBP and CD14 mRNA in a mouse model of sepsis.  J Surg Res. 1998;  76 67-73
    CrossrefPubMedGoogle Scholar
  • 129 Malloy J, Mccaig L, Veldhuizen R et al.. Alterations of the endogenous surfactant system in septic adult rats.  Am J Respir Crit Care Med. 1997;  156 617-623
    PubMedGoogle Scholar
  • 130 Herbein J F, Wright J R. Enhanced clearance of surfactant protein D during LPS-induced acute inflammation in rat lung.  Am J Physiol Lung Cell Mol Physiol. 2001;  281 L268-L277
    PubMedGoogle Scholar
  • 131 Martin T R. Lung Cytokines and ARDS.  Chest. 1999;  116 2S-8S
    CrossrefPubMedGoogle Scholar
  • 132 Martin T R, Goodman R B. The role of chemokines in the pathophysiology of the acute respiratory distress syndrome (ARDS). In: Hebert CA Chemokines in Disease: Biology and Clinical Research. Totowa, NJ; Humana 1999: 81-110
    Google Scholar
  • 133 Martin T R, Matute-Bello G, Skerrett S J, Frevert C W. Extrapulmonary sepsis and cytokines in lung injury and defenses. In: Nelson S, Martin TR Cytokines in Pulmonary Disease: Infection and Inflammation. New York; Marcel Dekker 2000: 403-458
    Google Scholar
  • 134 Ware L B, Matthay M A. The acute respiratory distress syndrome.  N Engl J Med. 2000;  342 1334-1349
    CrossrefPubMedGoogle Scholar

Charles W FrevertD.V.M. Sc.D. 

VA Puget Sound Medical Center

GMR151-L, 1660 South Columbian Way

Seattle, WA

eMail: cfrevert@u.washington.edu

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