Sepsis: Molecular mechanisms underlying lipopolysaccharide recognition

Expert Reviews in Molecular Medicine

Volumn 6, Issue 4, 2004, Pages

  Triantafilou, Martha ^a   Triantafilou, Kathy ^a  

^a UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

Innate immunity; Lipopolysaccharide; LPS; Pattern recognition receptors; Peptidoglycan; Sepsis; Septic shock; Toll like receptors

Indexed keywords

ANTICOAGULANT AGENT; ANTIINFECTIVE AGENT; BACTERICIDAL PERMEABILITY INCREASING PROTEIN; BACTERIUM LIPOPOLYSACCHARIDE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CD11B ANTIGEN; CD14 ANTIGEN; CD18 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; CORTICOSTEROID; DECAY ACCELERATING FACTOR; GLYCOPROTEIN P 15095; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; IMMUNOGLOBULIN RECEPTOR; IMMUNOSTIMULATING AGENT; INTEGRIN; MEMBRANE PROTEIN; MONOCLONAL ANTIBODY; NITRIC OXIDE SYNTHASE INHIBITOR; PATTERN RECOGNITION RECEPTOR; PHOSPHOLIPASE A2 INHIBITOR; PLASMA PROTEIN; PROTEIN NOD1; PROTEIN RP105; PROTEIN TREM 1; SCAVENGER RECEPTOR; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; UNCLASSIFIED DRUG; UNINDEXED DRUG; CELL SURFACE RECEPTOR; LIPOPOLYSACCHARIDE;

BACTERIAL INFECTION; CLINICAL TRIAL; DRUG DESIGN; DRUG TARGETING; FATALITY; HOST RESISTANCE; HUMAN; INNATE IMMUNITY; LIPID RAFT; NONHUMAN; PRIORITY JOURNAL; REVIEW; SEPSIS; SEPTIC SHOCK; IMMUNOLOGY; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

BACTERIA (MICROORGANISMS);

BLOOD PROTEINS; CLINICAL TRIALS; HUMANS; IMMUNITY, NATURAL; LIPOPOLYSACCHARIDES; RECEPTORS, CELL SURFACE; SEPSIS; SIGNAL TRANSDUCTION;

EID: 31044445841     PISSN: 14623994     EISSN: None     Source Type: Journal    
DOI: 10.1017/S1462399404007654     Document Type: Review

References (132)

1. Angus, D.C. et al. (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29, 1303-1310
2. Medzhitov, R. and Janeway, C.A., Jr. (1998) An ancient system of host defense. Curr Opin Immunol 10, 12-15
3. Alexopoulou, L. et al. (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732-738
4. Elsbach, P. and Weiss, J. (1993) The bactericidal/ permeability-increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide. Immunobiology 187, 417-429
5. Tobias, P.S. et al. (1997) Lipopolysaccharide (LPS)-binding proteins BPI and LBP form different types of complexes with LPS. J Biol Chem 272, 18682-18685
6. Hubsch, A.P. et al. (1993) A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. Circ Shock 40, 14-23
7. de Bont, N. et al. (1999) Apolipoprotein E knockout mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J Lipid Res 40, 680-685
8. Elass-Rochard, E. et al. (1998) Lactoferrin inhibits the endotoxin interaction with CD14 by competition with the lipopolysaccharide-binding protein. Infect Immun 66, 486-491
9. Wright, S.D. et al. (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431-1433
10. Shimazu, R. et al. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189, 1777-1782
11. Akashi, S. et al. (2000) Cutting edge: cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages. J Immunol 164, 3471-3475
12. Weinstein, S.L., Gold, M.R. and DeFranco, A.L. (1991) Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages. Proc Natl Acad Sci U S A 88, 4148-4152
13. Hambleton, J. et al. (1996) Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. Proc Natl Acad Sci U S A 93, 2774-2778
14. Swantek, J.L., Cobb, M.H. and Geppert, T.D. (1997) Jun N-terminal kinase/ stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. Mol Cell Biol 17, 6274-6282
15. O'Neill, L. (2000) The Toll/interleukin-1 receptor domain: a molecular switch for inflammation and host defence. Biochem Soc Trans 28, 557-563
16. Medzhitov, R. (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1, 135-145
17. Cario, E. (2003) Toll-like receptors and intestinal defence: molecular basis and therapeutic implications. Expert Rev Mol Med 5, 1-15
18. Akira, S. (2001) Toll-like receptors and innate immunity. Adv Immunol 78, 1-56
19. Lynn, W.A., Liu, Y. and Golenbock, D.T. (1993) Neither CD14 nor serum is absolutely necessary for activation of mononuclear phagocytes by bacterial lipopolysaccharide. Infect Immun 61, 4452-4461
20. Blondin, C. et al. (1997) Lipopolysaccharide complexed with soluble CD14 binds to normal human monocytes. Eur J Immunol 27, 3303-3309
21. Troelstra, A. et al. (1997) Saturable CD14-dependent binding of fluorescein-labeled lipopolysaccharide to human monocytes. Infect Immun 65, 2272-2277
22. Triantafilou, M., Triantafilou, K. and Fernandez, N. (2000) Rough and smooth forms of fluorescein-labelled bacterial endotoxin exhibit CD14/ LBP dependent and independent binding that is influencedby endotoxin concentration. Eur J Biochem 267, 2218-2226
23. Gessani, S. et al. (1993) Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages. Role of LPS receptors. J Immunol 151, 3758-3766
24. Hampton, R.Y. et al. (1991) Recognition and plasma clearance of endotoxin by scavenger receptors. Nature 352, 342-344
25. Ingalls, R.R. and Golenbock, D.T. (1995) CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med 181, 1473-1479
26. Ingalls, R.R., Arnaout, M.A. and Golenbock, D.T. (1997) Outside-in signaling by lipopolysaccharide through a tailless integrin. J Immunol 159, 433-438
27. Medvedev, A.E. et al. (1998) Involvement of CD14 and complement receptors CR3 and CR4 in nuclear factor-kappaB activation and TNF production induced by lipopolysaccharide and group B streptococcal cell walls. J Immunol 160, 4535-4542
28. Chow, J.C. et al. (1999) Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 274, 10689-10692
29. Troelstra, A. et al. (1999) Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18. J Immunol 162, 4220-4225
30. Ingalls, R.R. et al. (1998) CD11/CD18 and CD14 share a common lipid A signaling pathway. J Immunol 161, 5413-5420
31. Heine, H. et al. (2001) Decay-accelerating factor (DAF/CD55) is a functional active element of the LPS receptor complex. J Endotoxin Res 7, 227-231
32. Heine, H. et al. (2003) CD55/decay accelerating factor is part of the lipopolysaccharide-induced receptor complex. Eur J Immunol 33, 1399-1408
33. Pfeiffer, A. et al. (2001) Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. Eur J Immunol 31, 3153-3164
34. Bouchon, A., Dietrich, J. and Colonna, M. (2000) Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164, 4991-4995
35. Bouchon, A. et al. (2001) TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 410, 1103-1107
36. Miyake, K. et al. (1995) RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family. J Immunol 154, 3333-3340
37. Ogata, H. et al. (2000) The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells. J Exp Med 192, 23-29
38. Miyake, K. et al. (2000) Innate recognition of lipopolysaccharide by Toll-like receptor 4/MD-2 and RP105/MD-1. J Endotoxin Res 6, 389-391
39. Nagai, Y. et al. (2002) Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood 99, 1699-1705
40. Byrd, C.A. et al. (1999) Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide. Proc Natl Acad Sci U S A 96, 5645-5650
41. Triantafilou, K., Triantafilou, M. and Dedrick, R.L. (2001) A CD14-independent LPS receptor cluster. Nat Immunol 2, 338-345
42. Kaur, I. et al. (1993) Human peripheral gamma delta T cells recognize hsp60 molecules on Daudi Burkitt's lymphoma cells. J Immunol. 150, 2046-2055
43. Multhoff, G. et al. (1997) Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol 158, 4341-4350
44. Tsuboi, N. et al. (1994) Monoclonal antibody specifically reacting against 73-kilodalton heat shock cognate protein: possible expression on mammalian cell surface. Hybridoma. 13, 373-381
45. Tamura, Y. et al. (1993) 70 kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's anti-tumor immunity. J Immunol 151, 5516-5524
46. Todryk, S.M. et al. (2000) Heat shock proteins refine the danger theory. Immunology 99, 334-337
47. Vabulas, R.M. et al. (2002) HSP70 as endogenous stimulus of the Toll/ interleukin-1 receptor signal pathway. J Biol Chem 277, 15107-15112
48. Vabulas, R.M. et al. (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276, 31332-31339
49. Vabulas, R.M. et al. (2002) The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J Biol Chem 277, 20847-20853
50. Zhu, F.G. and Pisetsky, D.S. (2001) Role of the heat shock protein 90 in immune response stimulation by bacterial DNA and synthetic oligonucleotides. Infect Immun 69, 5546-5552
51. Bandholtz, L. et al. (2003) Hsp90 binds CpG oligonucleotides directly: implications for hsp90 as a missing link in CpG signaling and recognition. Cell Mol Life Sci 60, 422-429
52. Triantafilou, M. et al. (2002) Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation. J Cell Sci 115, 2603-2611
53. Broquet, A.H. et al. (2003) Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J Biol Chem 278, 21601-21606
54. Asea, A. et al. (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6, 435-442
55. Gao, B. and Tsan, M.F. (2003) Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages. J Biol Chem 278, 174-179
56. Moriuchi, M. et al. (1998) Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1. J Clin Invest 102, 1540-1550
57. Deng, H. et al. (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661-666
58. Feng, Y. et al. (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872-877
59. Juffermans, N.P. et al. (2000) Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines. Blood 96, 2649-2654
60. Inohara, N. et al. (2001) Human Nod1 confers responsiveness to bacterial lipopolysaccharides. J Biol Chem 276, 2551-2554
61. Chamaillard, M. et al. (2003) An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 4, 702-707
62. Girardin, S.E. et al. (2003) Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300, 1584-1587
63. Girardin, S.E. et al. (2003) Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J Biol Chem 278, 41702-41708
64. Girardin, S.E. et al. (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278, 8869-8872
65. Gutierrez, O. et al. (2002) Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem 277, 41701-41705
66. Hugot, J.P. et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599-603
67. Ogura, Y. et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603-606
68. Perera, P.Y. et al. (2001) CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J Immunol 166, 574-581
69. Ozinsky, A. et al. (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A 97, 13766-13771
70. Hajjar, A.M. et al. (2001) Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J Immunol 166, 15-19
71. Anderson, H.A., Hiltbold, E.M. and Roche, P.A. (2000) Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol 1, 156-162
72. Pralle, A. et al. (2000) Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol 148, 997-1008
73. Wang, P.Y., Kitchens, R.L. and Munford, R.S. (1995) Bacterial lipopolysaccharide binds to CD14 in low-density domains of the monocyte-macrophage plasma membrane. J Inflamm 47, 126-137
74. Latz, E. et al. (2002) Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction. J Biol Chem 277, 47834-47843
75. Hotchkiss, R.S. and Karl, I.E. (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348, 138-150
76. Wheeler, A.P. and Bernard, G.R. (1999) Treating patients with severe sepsis. N Engl J Med 340, 207-214
77. Bulger, E.M. and Maier, R.V. (2000) Lipid mediators in the pathophysiology of critical illness. Crit Care Med 28, N27-36
78. Zimmerman, G.A. et al. (2002) The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 30, S294-301
79. Carvalho, A.C. and Freeman, N.J. (1994) How coagulation defects alter outcome in sepsis: survival may depend on reversing procoagulant conditions. J Crit Illness 9, 51-75
80. Levi, M. and Ten Cate, H. (1999) Disseminated intravascular coagulation. N Engl J Med 341, 586-592
81. Ziegler, E.J. et al. (1991) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med 324, 429-436
82. Alejandria, M.M. et al. (2002) Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev CD001090
83. Goeddel, D.V (1999) Signal transduction by tumor necrosis factor: the Parker B. Francis Lectureship. Chest 116, 69S-73S
84. Abraham, E. et al. (2001) Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients. Crit Care Med 29, 503-510
85. Fisher, C.J., Jr. et al. (1993) Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group. Crit Care Med 21, 318-327
86. Abraham, E. et al. (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. Jama 273, 934-941
87. Cohen, J. and Carlet, J. (1996) INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 24, 1431-1440
88. Abraham, E. et al. (1998) Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 351, 929-933
89. Clark, M.A. et al. (1998) Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis - a randomized, clinical trial. Crit Care Med 26, 1650-1659
90. Penacek, E.A. et al. (2000) Neutralisation of TNF by a monoclonal antibody improves survival and reduces organ dysfunction in human sepsis: Results of the MONARCS trial. Chest 116, S88
91. Gallagher, J. et al. (2001) A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome. Intensive Care Med 27, 1169-1178
92. Fisher, C.J., Jr. et al. (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. Jama 271, 1836-1843
93. Opal, S.M. et al. (1997) Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med 25, 1115-1124
94. Levin, M. et al. (2000) Recombinant bactericidal/permeability-increasing protein (rBP121) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 356, 961-967
95. Larrick, J.W. et al. (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63, 1291-1297
96. Flegel, W.A. et al. (1989) Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun 57, 2237-2245
97. Hanasawa, K. (2002) Extracorporeal treatment for septic patients: new adsorption technologies and their clinical application. Ther Apher 6, 290-295
98. Uhl, W. et al. (1995) A multicenter study of phospholipase A2 in patients in intensive care units. J Am Coll Surg 180, 323-331
99. Springer, D.M. (2001) An update on inhibitors of human 14 kDa Type II s-PLA2 in development. Curr Pharm Des 7, 181-198
100. Dhainaut, J.F. et al. (1994) Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group. Crit Care Med 22, 1720-1728
101. Johnson, C.D. et al. (2001) Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut 48, 62-69
102. Poeze, M. et al. (2000) Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group. Shock 14, 421-428
103. Schuster, D.P. et al. (2003) Recombinant platelet-activating factor acetylhydrolase to prevent acute respiratory distress syndrome and mortality in severe sepsis: Phase IIb, multicenter, randomized, placebo-controlled, clinical trial. Crit Care Med 31, 1612-1619
104. Grover, R. et al. (1999) An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group. Crit Care Med 27, 913-922
105. Root, R.K. et al. (2003) Multicenter, double-blind, placebo-controlled study of the use of filgrastim, in patients hospitalized with pneumonia and severe sepsis. Crit Care Med 31, 367-373
106. Gregory, S.A., Morrissey, J.H. and Edgington, T.S. (1989) Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 9, 2752-2755
107. Smith, O.P. et al. (1997) Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet 350, 1590-1593
108. Bernard, G.R. et al. (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344, 699-709
109. Warren, B.L. et al. (2001) Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. Jama 286, 1869-1878
110. Abraham, E. (2000) Tissue factor inhibition and clinical trial results of tissue factor pathway inhibitor in sepsis. Crit Care Med 28, S31-33
111. Jilma, B. et al. (2002) Pharmacodynamics of active site-inhibited factor VIIa in endotoxin-induced coagulation in humans. Clin Pharmacol Ther 72, 403-410
112. Schumer, W. (1976) Steroids in the treatment of clinical septic shock. Ann Surg 184, 333-341
113. Bone, R.C. et al. (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317, 653-658
114. Cronin, L. et al. (1995) Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23, 1430-1439
115. Annane, D. et al. (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Jama 288, 862-871
116. Loppnow, H. et al. (1990) Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by nontoxic Rhodobacter capsulatus LPS. Infect Immun 58, 3743-3750
117. Rose, J.R. et al. (1995) Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: comparison with activities of synthetic material of the proposed structure and analogs. Infect Immun 63, 833-839
118. Rietschel, E.T. et al. (1996) Bacterial endotoxin: Chemical constitution, biological recognition, host response, and immunological detoxification. Curr Top Microbiol Immunol 216, 39-81
119. Loppnow, H. et al. (1989) IL-1 induction-capacity of defined lipopolysaccharide partial structures. J Immunol 142, 3229-3238
120. Golenbock, D.T. et al. (1991) Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem 266, 19490-19498
121. Christ, W.J. et al. (1995) E5531, a pure endotoxin antagonist of high potency. Science 268, 80-83
122. Kawata, T. et al. (1999) E5531, a synthetic nontoxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide. Br J Pharmacol 127, 853-862
123. Marshall, J.C. (2003) Such stuff as dreams are made on: mediator-directed therapy in sepsis. Nat Rev Drug Discov 2, 391-405
124. Mancuso, G. et al. (2002) Mitogen-activated protein kinases and NF-kappa B are involved in TNF-alpha responses to group B streptococci. J Immunol 169, 1401-1409
125. Beutler, B. and Rehli, M. (2002) Evolution of the TIR, tolls and TLRs: functional inferences from computational biology. Curr Top Microbiol Immunol 270, 1-21
126. Kawai, T. et al. (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115-122
127. Horng, T., Barton, G.M. and Medzhitov, R. (2001) TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol 2, 835-841
128. Horng, T. et al. (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420, 329-333
129. Hoebe, K. et al. (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424, 743-748
130. Poltorak, A. et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/ 10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088
131. Wright, S.D. and Jong, M.T. (1986) Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J Exp Med 164, 1876-1888
132. Nathan, C. and Ding, A. (2001) TREM-1: a new regulator of innate immunity in sepsis syndrome. Nat Med 7, 530-532