Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?

Journal of Biomedical Science

Volumn 18, Issue 1, 2011, Pages

  Neher, Miriam D ^a   Weckbach, Sebastian ^a   Flierl, Michael A ^a   Huber Lang, Markus S ^b   Stahel, Philip F ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C3A; COMPLEMENT COMPONENT C5; COMPLEMENT COMPONENT C5A; COMPLEMENT COMPONENT C5A RECEPTOR; PROPERDIN; THROMBIN; COMPLEMENT;

ACUTE LUNG INJURY; ADULT RESPIRATORY DISTRESS SYNDROME; COMPLEMENT ACTIVATION; HUMAN; INFLAMMATION; MOLECULAR MECHANICS; MULTIPLE TRAUMA; MUSCULOSKELETAL INJURY; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SEPSIS; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; THORAX INJURY; TISSUE INJURY; TRAUMATIC BRAIN INJURY; ANIMAL; IMMUNOLOGY; INJURY; INNATE IMMUNITY; PHYSIOLOGY;

ANIMALS; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM PROTEINS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; WOUNDS AND INJURIES;

EID: 82255195370     PISSN: 10217770     EISSN: 14230127     Source Type: Journal    
DOI: 10.1186/1423-0127-18-90     Document Type: Review

References (201)

1. Current trends in resuscitation strategy for the multiply injured patient. Stahel PF, Smith WR, Moore EE, Injury 2009 40 SUPPL. 4 27 35
2. Trauma and long-term mortality. Rahimi-Movaghar V, Rasouli MR, Vaccaro AR, JAMA 2011 305 23 2413 2414 author reply 2413
3. Injury mortality indicators: recommendations from the International Collaborative Effort on Injury Statistics. Cryer C, Fingerhut L, Segui-Gomez M, Inj Prev 2011 17 4 281 284
4. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Kauvar DS, Wade CE, Crit Care 2005 9 SUPPL. 5 1 9
5. Polytrauma-pathophysiology and management principles. Gebhard F, Huber-Lang M, Langenbecks Arch Surg 2008 393 6 825 831
6. Pathophysiology of polytrauma. Keel M, Trentz O, Injury 2005 36 6 691 709 (Pubitemid 40732303)
7. Role of biological modifiers regulating the immune response after trauma. Stahel PF, Smith WR, Moore EE, Injury 2007 38 12 1409 1422 (Pubitemid 350192403)
8. Interactions between coagulation and complement-their role in inflammation. Oikonomopoulou K, Ricklin D, Ward PA, Lambris JD, Semin Immunopathol 2011
9. Multiple trauma induces serum production of host defence peptides. Lippross S, Klueter T, Steubesand N, Oestern S, Mentlein R, Hildebrandt F, Podschun R, Pufe T, Seekamp A, Varoga D, Injury 2011
10. Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Bellander BM, Olafsson IH, Ghatan PH, Bro Skejo HP, Hansson LO, Wanecek M, Svensson MA, Acta Neurochir (Wien) 2011 153 1 90 100
11. Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Griffiths M, Neal JW, Gasque P, Int Rev Neurobiol 2007 82 29 55
12. The role of the complement system in traumatic brain injury. Stahel PF, Morganti-Kossmann MC, Kossmann T, Brain Res Brain Res Rev 1998 27 3 243 256 (Pubitemid 28389310)
13. Activation of the clotting system and complement after trauma. Dries DJ, New Horiz 1996 4 2 276 288 (Pubitemid 26171434)
14. Trauma: the role of the innate immune system. Hietbrink F, Koenderman L, Rijkers G, Leenen L, World J Emerg Surg 2006 1 15
15. Immunology. Dangers in and out. Bianchi ME, Manfredi AA, Science 2009 323 5922 1683 1684
16. The role of complement in danger sensing and transmission. Köhl J, Immunol Res 2006 34 2 157 176 (Pubitemid 43997968)
17. DAMPs, PAMPs and alarmins: all we need to know about danger. Bianchi ME, J Leukoc Biol 2007 81 1 1 5 (Pubitemid 46028489)
18. DAMPs and inflammatory processes: the role of redox in the different outcomes. Carta S, Castellani P, Delfino L, Tassi S, Vene R, Rubartelli A, J Leukoc Biol 2009 86 3 549 555
19. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. Foell D, Wittkowski H, Vogl T, Roth J, J Leukoc Biol 2007 81 1 28 37 (Pubitemid 46021248)
20. Heat shock protein 60 (HSP60) stimulates neutrophil effector functions. Osterloh A, Geisinger F, Piedavent M, Fleischer B, Brattig N, Breloer M, J Leukoc Biol 2009 86 2 423 434
21. The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation. McGhan LJ, Jaroszewski DE, Injury 2011
22. The impact of endogenous triggers on trauma-associated inflammation. Zedler S, Faist E, Curr Opin Crit Care 2006 12 6 595 601 (Pubitemid 44673437)
23. The role of the complement system in CNS inflammatory diseases. Stahel PF, Barnum SR, Expert Rev Clin Immunol 2006 2 3 445 456 (Pubitemid 44355575)
24. "Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Elward K, Gasque P, Mol Immunol 2003 40 2-4 85 94 (Pubitemid 36959819)
25. The regulation of the CNS innate immune response is vital for the restoration of tissue homeostasis (repair) after acute brain injury: a brief review. Griffiths MR, Gasque P, Neal JW, Int J Inflam 2010 2010 151097
26. The multiple roles of the innate immune system in the regulation of apoptosis and inflammation in the brain. Griffiths MR, Gasque P, Neal JW, J Neuropathol Exp Neurol 2009 68 3 217 226
27. The complement cascade: Yin-Yang in neuroinflammation - neuro-protection and -degeneration. Alexander JJ, Anderson AJ, Barnum SR, Stevens B, Tenner AJ, J Neurochem 2008 107 5 1169 1187
28. Role of C5a in inflammatory responses. Guo RF, Ward PA, Annu Rev Immunol 2005 23 821 852 (Pubitemid 40563186)
29. Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Nataf S, Stahel PF, Davoust N, Barnum SR, Trends Neurosci 1999 22 9 397 402 (Pubitemid 29453644)
30. Complement: structure, functions, evolution, and viral molecular mimicry. Mastellos D, Morikis D, Isaacs SN, Holland MC, Strey CW, Lambris JD, Immunol Res 2003 27 2-3 367 386
31. The role of the anaphylatoxins in health and disease. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J, Mol Immunol 2009 46 14 2753 2766
32. Complement: a key system for immune surveillance and homeostasis. Ricklin D, Hajishengallis G, Yang K, Lambris JD, Nat Immunol 2010 11 9 785 797
33. The effect of trauma on serum C3 activation and its correlation with injury severity score in man. Kapur MM, Jain P, Gidh M, J Trauma 1986 26 5 464 466 (Pubitemid 16063760)
34. Estimation of serum complement and its role in management of trauma. Kapur MM, Jain P, Gidh M, World J Surg 1988 12 2 211 216
35. Nitric oxide and redox mechanisms in the immune response. Wink DA, Hines HB, Cheng RY, Switzer CH, Flores-Santana W, Vitek MP, Ridnour LA, Colton CA, J Leukoc Biol 2011 89 6 873 891
36. Trauma Activated Polymorphonucleated Leukocytes Damage Endothelial Progenitor Cells. Probable Role of CD11b/CD18-CD54 Interaction and Release of Reactive Oxygen Species. Henrich D, Zimmer S, Seebach C, Frank J, Barker J, Marzi I, Shock 2011
37. Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of alveolar macrophages and neutrophils. Seitz DH, Perl M, Mangold S, Neddermann A, Braumuller ST, Zhou S, Bachem MG, Huber-Lang MS, Knoferl MW, Shock 2008 30 5 537 544
38. Postinjury neutrophil priming and activation: an early vulnerable window. Botha AJ, Moore FA, Moore EE, Kim FJ, Banerjee A, Peterson VM, Surgery 1995 118 2 358 364 discussion 364-355
39. Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. Partrick DA, Moore FA, Moore EE, Barnett CC Jr, Silliman CC, New Horiz 1996 4 2 194 210 (Pubitemid 26171429)
40. Inflammatory response in acute traumatic brain injury: a double-edged sword. Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T, Curr Opin Crit Care 2002 8 2 101 105 (Pubitemid 36132681)
41. Complement and immune defense: from innate immunity to human diseases. Zipfel PF, Immunol Lett 2009 126 1-2 1 7
42. Complement in inflammatory tissue damage and disease. Mollnes TE, Song WC, Lambris JD, Trends Immunol 2002 23 2 61 64 (Pubitemid 34310141)
43. Inhibition of complement as a therapeutic approach in inflammatory central nervous system (CNS) disease. Barnum SR, Mol Med 1999 5 9 569 582 (Pubitemid 32936948)
44. Complement: a unique innate immune sensor for danger signals. Gasque P, Mol Immunol 2004 41 11 1089 1098 (Pubitemid 39345390)
45. The evolution, structure, biology and pathophysiology of complement. Lambris JD, Reid KB, Volanakis JE, Immunol Today 1999 20 5 207 211 (Pubitemid 29217075)
46. Function, structure and therapeutic potential of complement C5a receptors. Monk PN, Scola AM, Madala P, Fairlie DP, Br J Pharmacol 2007 152 4 429 448 (Pubitemid 47585036)
47. Anaphylatoxins: their role in bacterial infection and inflammation. Haas PJ, van Strijp J, Immunol Res 2007 37 3 161 175 (Pubitemid 47577440)
48. The dark side of C5a in sepsis. Ward PA, Nat Rev Immunol 2004 4 2 133 142 (Pubitemid 38209207)
49. Macrophage complement receptors and pathogen clearance. van Lookeren Campagne M, Wiesmann C, Brown EJ, Cell Microbiol 2007 9 9 2095 2102 (Pubitemid 47250283)
50. The complement system in trauma-related and ischemic tissue damage: a brief review. Mollnes TE, Fosse E, Shock 1994 2 4 301 310
51. Regulation of the complement membrane attack pathway. Morgan BP, Crit Rev Immunol 1999 19 3 173 198 (Pubitemid 29321438)
52. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. Spitzer D, Mitchell LM, Atkinson JP, Hourcade DE, J Immunol 2007 179 4 2600 2608
53. Generation of C5a in the absence of C3: a new complement activation pathway. Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, et al. Nat Med 2006 12 6 682 687 (Pubitemid 43865238)
54. Molecular intercommunication between the complement and coagulation system. Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Bruckner UB, Nilsson UB, Gebhard F, Lambris JD, et al. J Immunol 2010 185 9 5628 5636
55. Epidemiology, severity classification, and outcome of moderate and severe traumatic brain injury: a prospective multicenter study. Andriessen TM, Horn J, Franschman G, van der Naalt J, Haitsma I, Jacobs B, Steyerberg EW, Vos PE, J Neurotrauma 2011
56. Current trends in neurotrauma care. Timmons SD, Crit Care Med 2010 38 9 SUPPL. 431 444
57. Management of traumatic brain injury. Losiniecki A, Shutter L, Curr Treat Options Neurol 2010 12 2 142 154
58. Complement in the brain. Veerhuis R, Nielsen HM, Tenner AJ, Mol Immunol 2011 48 1592 1603
59. C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice. Longhi L, Perego C, Ortolano F, Zanier ER, Bianchi P, Stocchetti N, McIntosh TK, MG DS, Crit Care Med 2009 37 2 659 665
60. Complement components of the innate immune system in health and disease in the CNS. Gasque P, Dean YD, McGreal EP, VanBeek J, Morgan BP, Immunopharmacology 2000 49 1-2 171 186 (Pubitemid 30445228)
61. Complement in central nervous system inflammation. Barnum SR, Immunol Res 2002 26 1-3 7 13 (Pubitemid 35177479)
62. Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury. Stahel PF, Morganti-Kossmann MC, Perez D, Redaelli C, Gloor B, Trentz O, Kossmann T, J Neurotrauma 2001 18 8 773 781 (Pubitemid 32769773)
63. Complement biosynthesis in the central nervous system. Barnum SR, Crit Rev Oral Biol Med 1995 6 2 132 146
64. Complement activation in the central nervous system following blood-brain barrier damage in man. Lindsberg PJ, Ohman J, Lehto T, Karajalainen-Lindsberg ML, Paetau A, Wuorimaa T, Carpen O, Kaste M, Meri S, Ann Neurol 40 587 596
65. Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. Kossmann T, Stahel PF, Morganti-Kossmann MC, Jones JL, Barnum SR, J Neuroimmunol 1997 73 1-2 63 69 (Pubitemid 27105270)
66. Local neutrophil influx following lateral fluid-percussion brain injury in rats is associated with accumulation of complement activation fragments of the third component (C3) of the complement system. Keeling KL, Hicks RR, Mahesh J, Billings BB, Kotwal GJ, J Neuroimmunol 2000 105 1 20 30 (Pubitemid 30125425)
67. Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist. Sewell DL, Nacewicz B, Liu F, Macvilay S, Erdei A, Lambris JD, Sandor M, Fabry Z, J Neuroimmunol 2004 155 1-2 55 63 (Pubitemid 39165777)
68. Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. Kaczorowski SL, Schiding JK, Toth CA, Kochanek PM, J Cereb Blood Flow Metab 1995 15 5 860 864
69. Vaccinia virus complement control protein enhances functional recovery after traumatic brain injury. Hicks RR, Keeling KL, Yang MY, Smith SA, Simons AM, Kotwal GJ, J Neurotrauma 2002 19 6 705 714 (Pubitemid 34761334)
70. Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. Rancan M, Morganti-Kossmann MC, Barnum SR, Saft S, Schmidt OI, Ertel W, Stahel PF, J Cereb Blood Flow Metab 2003 23 9 1070 1074 (Pubitemid 37082432)
71. Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Leinhase I, Schmidt OI, Thurman JM, Hossini AM, Rozanski M, Taha ME, Scheffler A, John T, Smith WR, Holers VM, et al. Exp Neurol 2006 199 2 454 464 (Pubitemid 44202458)
72. Vaccinia virus complement control protein significantly improves sensorimotor function recovery after severe head trauma. Pillay NS, Kellaway LA, Kotwal GJ, Brain Res 2007 1153 158 165 (Pubitemid 46802530)
73. Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. Stahel PF, Kariya K, Shohami E, Barnum SR, Eugster H, Trentz O, Kossmann T, Morganti-Kossmann MC, J Neuroimmunol 2000 109 2 164 172
74. Inhibiting the C5-C5a receptor axis. Woodruff TM, Nandakumar KS, Tedesco F, Mol Immunol 2011 48 14 1631 1642
75. Complement anaphylatoxin C3a is selectively neuroprotective against NMDA-induced neuronal cell death. van Beek J, Nicole O, Ali C, Ischenko A, MacKenzie ET, Buisson A, Fonatine M, Neuroreport 2001 12 2 289 293 (Pubitemid 32114367)
76. Inflammatory signals induce neurtrophin expression in human microglial cells. Heese K, Hock C, Otten U, J Neurochem 1998 70 2 699 707 (Pubitemid 28079359)
77. Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection. van Beek J, Elward K, Gasque P, Ann N Y Acad Sci 2003 992 56 71 (Pubitemid 36706637)
78. Complement activation: beneficial and detrimental effects in the CNS. van Beek J, Ernst Schering Res Found Workshop 2004 47 67 85
79. Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. Leinhase I, Holers VM, Thurman JM, Harhausen D, Schmidt OI, Pietzcker M, Taha ME, Rittirsch D, Huber-Lang M, Smith WR, et al. BMC Neurosci 2006 7 55
80. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice. Leinhase I, Rozanski M, Harhausen D, Thurman JM, Schmidt OI, Hossini AM, Taha ME, Rittirsch D, Ward PA, Holers VM, et al. J Neuroinflammation 2007 4 13
81. Reduced tissue damage and improved recovery of motor function after traumatic brain injury in mice deficient in complement component C4. You Z, Yang J, Takahashi K, Yager PH, Kim HH, Qin T, Stahl GL, Ezekowitz RA, Carroll MC, Whalen MJ, J Cereb Blood Flow Metab 2007 27 12 1954 1964 (Pubitemid 350129164)
82. Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. Yager PH, You Z, Qin T, Kim HH, Takanashi K, Ezekowitz AB, Stahl GL, Carroll MC, Whalen MJ, J Cereb Blood Flow Metab 2008 28 5 1030 1039 (Pubitemid 351589641)
83. The alternative pathway of complement in disease: opportunities for therapeutic targeting. Holers VM, Thurman JM, Mol Immunol 2004 41 147 152 (Pubitemid 38668624)
84. Intracerebroventricular injection of the terminal complement complex causes inflammatory reaction in the rat brain. Casarsa C, De Luigi A, Pausa M, De Simoni MG, Tedesco F, Eur J Immunol 2003 33 5 1260 1270 (Pubitemid 36609144)
85. Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. Xiong ZQ, Qian W, Suzuki K, McNamara JO, J Neurosci 2003 23 3 955 960 (Pubitemid 36206186)
86. Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. Bellander BM, von Holst H, Fredman P, Svensson M, J Neurosurg 1996 85 3 468 475 (Pubitemid 26278030)
87. Complement activation in the human brain after traumatic head injury. Bellander BM, Singhrao SK, Ohlsson M, Mattsson P, Svensson M, J Neurotrauma 2001 18 12 1295 1311 (Pubitemid 34038404)
88. Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. Stahel PF, Flierl MA, Morgan BP, Persigehl I, Stoll C, Conrad C, Touban BM, Smith WR, Beauchamp K, Schmidt OI, et al. J Neuroinflammation 2009 6 2
89. Differential expression of individual complement regulators in the brain and choroid plexus. Singhrao SK, Neal JW, Rushmere NK, Morgan BP, Gasque P, Lab Invest 1999 79 10 1247 1259 (Pubitemid 29489449)
90. Increased phospholipase C activity after experimental brain injury. Wei EP, Lamb RG, Kontos HA, J Neurosurg 1982 56 5 695 698 (Pubitemid 12095050)
91. Pharmacology of traumatic brain injury: where is the "golden bullet"? Beauchamp K, Mutlak H, Smith WR, Shohami E, Stahel PF, Mol Med 2008 14 11-12 731 740
92. Complement therapeutics; history and current progress. Morgan BP, Harris CL, Mol Immunol 2003 40 2-4 159 170 (Pubitemid 36959825)
93. Tailoring anti-complement therapeutics. Harris CL, Fraser DA, Morgan BP, Biochem Soc Trans 2002 30 Pt 6 1019 1026 (Pubitemid 36002399)
94. Recent developments in low molecular weight complement inhibitors. Qu H, Ricklin D, Lambris JD, Mol Immunol 2009 47 2-3 185 195
95. Postinjury multiple organ failure. Dewar D, Moore FA, Moore EE, Balogh Z, Injury 2009 40 9 912 918
96. The role of the lung in postinjury multiple organ failure. Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC, Sauaia A, Surgery 2005 138 4 749 757 discussion 757-748
97. The two-event construct of postinjury multiple organ failure. Moore EE, Moore FA, Harken AH, Johnson JL, Ciesla D, Banerjee A, Shock 2005 24 SUPPL. 1 71 74
98. Lung injury severity scoring in the era of lung protective mechanical ventilation: the PaO2/FIO2 ratio. Offner PJ, Moore EE, J Trauma 2003 55 2 285 289 (Pubitemid 37047398)
99. [Emergency management of thoracic trauma]. Stahel PF, Schneider P, Buhr HJ, Kruschewski M, Orthopade 2005 34 9 865 879
100. Alveolar Macrophage Phagocytosis is Enhanced After Blunt Chest Trauma and Alters the Posttraumatic Mediator Release. Seitz DH, Palmer A, Niesler U, Froba JS, Heidemann V, Rittlinger A, Braumuller ST, Zhou S, Gebhard F, Knofer MW, Shock 2011
101. Is the function of alveolar macrophages altered following blunt chest trauma? Liener UC, Perl M, Huber-Lang MS, Seitz DH, Brückner UB, Gebhard F, Knöferl MW, Langenbecks Arch Surg 2011 396 2 251 259
102. Isolated blunt chest injury leads to transient activation of circulating neutrophils. Visser T, Hietbrink F, Groeneveld KM, Koenderman L, Leenen LP, Eur J Trauma Emerg Surg 2011 37 2 177 184
103. Blunt chest trauma induces mediator-dependent monocyte migration to the lung. Seitz DH, Niesler U, Palmer A, Sulger M, Braumuller ST, Perl M, Gebhard F, Knoferl MW, Crit Care Med 2010 38 9 1852 1859
104. The role of C5a in the innate immune response after experimental blunt chest trauma. Flierl MA, Perl M, Rittirsch D, Bartl C, Schreiber H, Fleig V, Schlaf G, Liener U, Brueckner UB, Gebhard F, et al. Shock 2008 29 1 25 31
105. Rous-Whipple Award Lecture. Role of complement in lung inflammatory injury. Ward PA, Am J Pathol 1996 149 4 1081 1086 (Pubitemid 26337226)
106. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement. Czermak BJ, Lentsch AB, Bless NM, Schmal H, Friedl HP, Ward PA, Am J Pathol 1999 154 5 1513 1524 (Pubitemid 29226446)
107. Chemotactic factor generation and cell accumulation in acute lung injury induced by endotracheal acid instillation. Ishii Y, Kobayashi J, Kitamura S, Prostaglandins Leukot Essent Fatty Acids 1989 37 1 65 70 (Pubitemid 19186234)
108. Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes. Kazmierowski JA, Gallin JI, Reynolds HY, J Clin Invest 1977 59 2 273 281 (Pubitemid 8055686)
109. Requirement and role of C5a in acute lung inflammatory injury in rats. Mulligan MS, Schmid E, Beck-Schimmer B, Till GO, Friedl HP, Brauer RB, Hugli TE, Miyasaka M, Warner RL, Johnson KJ, et al. J Clin Invest 1996 98 2 503 512 (Pubitemid 26255752)
110. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha. Czermak BJ, Sarma V, Bless NM, Schmal H, Friedl HP, Ward PA, J Immunol 1999 162 4 2321 2325 (Pubitemid 29288857)
111. Regulation of lung inflammation in the model of IgG immune-complex injury. Gao H, Neff T, Ward PA, Annu Rev Pathol 2006 1 215 242
112. NF-kappaB activation during IgG immune complex-induced lung injury: requirements for TNF-alpha and IL-1beta but not complement. Lentsch AB, Czermak BJ, Bless NM, Ward PA, Am J Pathol 1998 152 5 1327 1336 (Pubitemid 28221885)
113. Role of complement in in vitro and in vivo lung inflammatory reactions. Czermak BJ, Lentsch AB, Bless NM, Schmal H, Friedl HP, Ward PA, J Leukoc Biol 1998 64 1 40 48 (Pubitemid 28304672)
114. Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. Drouin SM, Kildsgaard J, Haviland J, Zabner J, Jia HP, McCray PB Jr, Tack BF, Wetsel RA, J Immunol 2001 166 3 2025 2032 (Pubitemid 32114691)
115. Expression and function of the C5a receptor in rat alveolar epithelial cells. Riedemann NC, Guo RF, Sarma VJ, Laudes IJ, Huber-Lang M, Warner RL, Albrecht EA, Speyer CL, Ward PA, J Immunol 2002 168 4 1919 1925 (Pubitemid 34135794)
116. Neurogenic amplification of immune complex inflammation. Bozic CR, Lu B, Hopken UE, Gerard C, Gerard NP, Science 1996 273 5282 1722 1725 (Pubitemid 26317790)
117. Selection of a C5a receptor antagonist from phage libraries attenuating the inflammatory response in immune complex disease and ischemia/reperfusion injury. Heller T, Hennecke M, Baumann U, Gessner JE, zu Vilsendorf AM, Baensch M, Boulay F, Kola A, Klos A, Bautsch W, et al. J Immunol 1999 163 2 985 994 (Pubitemid 29328111)
118. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease. Shushakova N, Skokowa J, Schulman J, Baumann U, Zwirner J, Schmidt RE, Gessner JE, J Clin Invest 2002 110 12 1823 1830 (Pubitemid 36076489)
119. A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. Ohno M, Hirata T, Enomoto M, Araki T, Ishimaru H, Takahashi TA, Mol Immunol 2000 37 8 407 412
120. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). Cain SA, Monk PN, J Biol Chem 2002 277 9 7165 7169 (Pubitemid 34953106)
121. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. Gerard NP, Lu B, Liu P, Craig S, Fujiwara Y, Okinaga S, Gerard C, J Biol Chem 2005 280 48 39677 39680 (Pubitemid 41779098)
122. Activator protein-1 activation in acute lung injury. Guo RF, Lentsch AB, Sarma JV, Sun L, Riedemann NC, McClintock SD, McGuire SR, Van Rooijen N, Ward PA, Am J Pathol 2002 161 1 275 282 (Pubitemid 34760793)
123. Stat3 activation in acute lung injury. Gao H, Guo RF, Speyer CL, Reuben J, Neff TA, Hoesel LM, Riedemann NC, McClintock SD, Sarma JV, Van Rooijen N, et al. J Immunol 2004 172 12 7703 7712 (Pubitemid 38747637)
124. An essential role for Stat3 in regulating IgG immune complex-induced pulmonary inflammation. Tang H, Yan C, Cao J, Sarma JV, Haura EB, Wu M, Gao H, FASEB J 2011
125. The acute respiratory distress syndrome. Ware LB, Matthay MA, N Engl J Med 2000 342 18 1334 1349 (Pubitemid 30408719)
126. Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome. Pathophysiological relevance and possible prognostic value. Hammerschmidt DE, Weaver LJ, Hudson LD, Craddock PR, Jacob HS, Lancet 1980 1 8175 947 949 (Pubitemid 10150800)
127. Complement and the severity of pulmonary failure. Weigelt JA, Chenoweth DE, Borman KR, Norcross JF, J Trauma 1988 28 7 1013 1019
128. Complement inhibitors selectively attenuate injury following administration of cobra venom factor to rats. Proctor LM, Strachan AJ, Woodruff TM, Mahadevan IB, Williams HM, Shiels IA, Taylor SM, Int Immunopharmacol 2006 6 8 1224 1232 (Pubitemid 43868182)
129. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Moore FA, Moore EE, Surg Clin North Am 1995 75 2 257 277
130. Impact of the complement cascade on posttraumatic cartilage inflammation and degradation. John T, Stahel PF, Morgan SJ, Schulze-Tanzil G, Histol Histopathol 2007 22 7 781 790 (Pubitemid 47034144)
131. New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System. Ehrnthaller C, Ignatius A, Gebhard F, Huber-Lang M, Mol Med 2011 17 3-4 317 329
132. C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. Schraufstatter IU, Discipio RG, Zhao M, Khaldoyanidi SK, J Immunol 2009 182 6 3827 3836
133. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Colter DC, Sekiya I, Prockop DJ, Proc Natl Acad Sci USA 2001 98 14 7841 7845 (Pubitemid 32642648)
134. [Method and conditions of isolation and proliferation of multipotent mesenchymal stem cells]. Tian X, Fu R, Deng L, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2007 21 1 81 85
135. Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro. Roman-Roman S, Garcia T, Jackson A, Theilhaber J, Rawadi G, Connolly T, Spinella-Jaegle S, Kawai S, Courtois B, Bushnell S, et al. Bone 2003 32 5 474 482 (Pubitemid 39665706)
136. C5a modulation of interleukin-1 beta-induced interleukin-6 production by human osteoblast-like cells. Pobanz JM, Reinhardt RA, Koka S, Sanderson SD, J Periodontal Res 2000 35 3 137 145
137. Transcriptional regulation of the production of the third component of complement (C3) by 1 alpha, 25-dihydroxyvitamin D3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells. Hong MH, Jin CH, Sato T, Ishimi Y, Abe E, Suda T, Endocrinology 1991 129 5 2774 2779
138. 1 alpha, 25-dihydroxyvitamin D3 regulates in vivo production of the third component of complement (C3) in bone. Jin CH, Shinki T, Hong MH, Sato T, Yamaguchi A, Ikeda T, Yoshiki S, Abe E, Suda T, Endocrinology 1992 131 5 2468 2475
139. The specific production of the third component of complement by osteoblastic cells treated with 1 alpha, 25-dihydroxyvitamin D3. Sato T, Hong MH, Jin CH, Ishimi Y, Udagawa N, Shinki T, Abe E, Suda T, FEBS Lett 1991 285 1 21 24
140. Complement and the recruitment of mononuclear osteoclasts. Mangham DC, Scoones DJ, Drayson MT, J Clin Pathol 1993 46 6 517 521 (Pubitemid 23209846)
141. Complement proteins are present in developing endochondral bone and may mediate cartilage cell death and vascularization. Andrades JA, Nimni ME, Becerra J, Eisenstein R, Davis M, Sorgente N, Exp Cell Res 1996 227 2 208 213 (Pubitemid 26320162)
142. Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody. Sakiyama H, Nakagawa K, Kuriiwa K, Imai K, Okada Y, Tsuchida T, Moriya H, Imajoh-Ohmi S, Cell Tissue Res 1997 288 3 557 565 (Pubitemid 27243827)
143. The Anaphylatoxin Receptor C5aR Is Present During Fracture Healing in Rats and Mediates Osteoblast Migration In Vitro. Ignatius A, Ehrnthaller C, Brenner RE, Kreja L, Schoengraf P, Lisson P, Blakytny R, Recknagel S, Claes L, Gebhard F, et al. J Trauma 2011
144. Predictors of reoperation following operative management of fractures of the tibial shaft. Bhandari M, Tornetta P, Sprague S, Najibi S, Petrisor B, Griffith L, Guyatt GH, J Orthop Trauma 2003 17 5 353 361 (Pubitemid 36701599)
145. Synthesis of classical pathway complement components by chondrocytes. Bradley K, North J, Saunders D, Schwaeble W, Jeziorska M, Woolley DE, Whaley K, Immunology 1996 88 4 648 656 (Pubitemid 26255139)
146. Complement C1s activation in degenerating articular cartilage of rheumatoid arthritis patients: immunohistochemical studies with an active form specific antibody. Nakagawa K, Sakiyama H, Tsuchida T, Yamaguchi K, Toyoguchi T, Masuda R, Moriya H, Ann Rheum Dis 1999 58 3 175 181 (Pubitemid 29172574)
147. Effect of IL-1beta, TNF-alpha and IL-4 on complement regulatory protein mRNA expression in human articular chondrocytes. Hyc A, Osiecka-Iwan A, Strzelczyk P, Moskalewski S, Int J Mol Med 2003 11 1 91 94
148. Immune deposits in articular cartilage of patients with rheumatoid arthritis have a granular pattern not seen in osteoarthritis. Vetto AA, Mannik M, Zatarain-Rios E, Wener MH, Rheumatol Int 1990 10 1 13 19 (Pubitemid 20160157)
149. Initiation of complement activation following oxidative stress. In vitro and in vivo observations. Hart ML, Walsh MC, Stahl GL, Mol Immunol 2004 41 2-3 165 171 (Pubitemid 38668626)
150. Complement mediators in ischemia-reperfusion injury. Arumugam TV, Magnus T, Woodruff TM, Proctor LM, Shiels IA, Taylor SM, Clin Chim Acta 2006 374 1-2 33 45 (Pubitemid 44572249)
151. The effect of ischemia reperfusion injury on skeletal muscle. Gillani S, Cao J, Suzuki T, Hak DJ, Injury 2011
152. Hypoxia and hypotension, the "lethal duo" in traumatic brain injury: implications for prehospital care. Stahel PF, Smith WR, Moore EE, Intensive Care Med 2008 34 3 402 404 (Pubitemid 351623022)
153. Terminal complement complexes and anaphylatoxins in septic and ischemic patients. Heideman M, Norder-Hansson B, Bengtson A, Mollnes TE, Arch Surg 1988 123 2 188 192 (Pubitemid 18069599)
154. Complement activation following oxidative stress. Collard CD, Lekowski R, Jordan JE, Agah A, Stahl GL, Mol Immunol 1999 36 13-14 941 948 (Pubitemid 30100846)
155. IgM binding to injured tissue precedes complement activation during skeletal muscle ischemia-reperfusion. Chan RK, Ding G, Verna N, Ibrahim S, Oakes S, Austen WG Jr, Hechtman HB, Moore FD Jr, J Surg Res 2004 122 1 29 35 (Pubitemid 39441229)
156. Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation. Holers VM, Kulik L, Mol Immunol 2007 44 1-3 64 72 (Pubitemid 44647113)
157. Complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies. Diepenhorst GM, van Gulik TM, Hack CE, Ann Surg 2009 249 6 889 899
158. Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM. Austen WG Jr, Zhang M, Chan R, Friend D, Hechtman HB, Carroll MC, Moore FD Jr, Surgery 2004 136 2 401 406 (Pubitemid 39037680)
159. The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia- reperfusion. Chan RK, Ibrahim SI, Takahashi K, Kwon E, McCormack M, Ezekowitz A, Carroll MC, Moore FD Jr, Austen WG Jr, J Immunol 2006 177 11 8080 8085 (Pubitemid 44846326)
160. Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. Weiser MR, Williams JP, Moore FD Jr, Kobzik L, Ma M, Hechtman HB, Carroll MC, J Exp Med 1996 183 5 2343 2348 (Pubitemid 26158925)
161. C1, MBL-MASPs and C1-inhibitor: novel approaches for targeting complement-mediated inflammation. Beinrohr L, Dobo J, Zavodszky P, Gal P, Trends Mol Med 2008 14 12 511 521
162. C1-esterase inhibitor and a novel peptide inhibitor improve contractile function in reperfused skeletal muscle. Toomayan GA, Chen LE, Jiang HX, Qi WN, Seaber AV, Frank MM, Urbaniak JR, Microsurgery 2003 23 6 561 567 (Pubitemid 38049965)
163. Moderation of skeletal muscle reperfusion injury by a sLe(x)-glycosylated complement inhibitory protein. Kyriakides C, Wang Y, Austen WG Jr, Favuzza J, Kobzik L, Moore FD Jr, Hechtman HB, Am J Physiol Cell Physiol 2001 281 1 224 230
164. Decay-accelerating factor attenuates remote ischemia-reperfusion- initiated organ damage. Weeks C, Moratz C, Zacharia A, Stracener C, Egan R, Peckham R, Moore FD Jr, Tsokos GC, Clin Immunol 2007 124 3 311 327 (Pubitemid 47247607)
165. Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion. Bless NM, Warner RL, Padgaonkar VA, Lentsch AB, Czermak BJ, Schmal H, Friedl HP, Ward PA, Am J Physiol 1999 276 1 Pt 1 57 63
166. Protective effects of a potent C5a receptor antagonist on experimental acute limb ischemia-reperfusion in rats. Woodruff TM, Arumugam TV, Shiels IA, Reid RC, Fairlie DP, Taylor SM, J Surg Res 2004 116 1 81 90 (Pubitemid 38083288)
167. Neutrophil mediated remote organ injury after lower torso ischemia and reperfusion is selectin and complement dependent. Kyriakides C, Austen WG Jr, Wang Y, Favuzza J, Moore FD Jr, Hechtman HB, J Trauma 2000 48 1 32 38 (Pubitemid 30054297)
168. Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex. Kyriakides C, Austen W Jr, Wang Y, Favuzza J, Kobzik L, Moore FD Jr, Hechtman HB, Am J Physiol 1999 277 6 Pt 1 1263 1268
169. Complement activation in injured patients occurs immediately and is dependent on the severity of the trauma. Fosse E, Pillgram-Larsen J, Svennevig JL, Nordby C, Skulberg A, Mollnes TE, Abdelnoor M, Injury 1998 29 7 509 514 (Pubitemid 28423365)
170. Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. Roumen RM, Redl H, Schlag G, Zilow G, Sandtner W, Koller W, Hendriks T, Goris RJ, Crit Care Med 1995 23 3 474 480
171. Role of the alternative pathway in the early complement activation following major trauma. Ganter MT, Brohi K, Cohen MJ, Shaffer LA, Walsh MC, Stahl GL, Pittet JF, Shock 2007 28 1 29 34 (Pubitemid 46956459)
172. Posttraumatic complications and inflammatory mediators. Nuytinck JK, Goris JA, Redl H, Schlag G, van Munster PJ, Arch Surg 1986 121 8 886 890 (Pubitemid 16039332)
173. Circulating complement proteins in multiple trauma patients - correlation with injury severity, development of sepsis, and outcome. Hecke F, Schmidt U, Kola A, Bautsch W, Klos A, Kohl J, Crit Care Med 1997 25 12 2015 2024 (Pubitemid 28007240)
174. The effect of recent trauma on serum complement activation and serum C3 levels correlated with the injury severity score. Sharma DK, Sarda AK, Bhalla SA, Goyal A, Kulshreshta VN, Indian J Med Microbiol 2004 22 3 147 152 (Pubitemid 39206735)
175. Early expression changes of complement regulatory proteins and C5a receptor (CD88) on leukocytes after multiple injury in humans. Amara U, Kalbitz M, Perl M, Flierl MA, Rittirsch D, Weiss M, Schneider M, Gebhard F, Huber-Lang M, Shock 2010 33 6 568 575
176. Anaphylatoxin formation in sepsis. Bengtson A, Heideman M, Arch Surg 1988 123 5 645 649
177. Sepsis, apoptosis and complement. Ward PA, Biochem Pharmacol 2008 76 11 1383 1388
178. Serum complement levels and severity of sepsis. Nakae H, Endo S, Inada K, Takakuwa T, Kasai T, Yoshida M, Res Commun Chem Pathol Pharmacol 1994 84 2 189 195
179. Complement C5a in the sepsis syndrome - too much of a good thing? Gerard C, N Engl J Med 2003 348 2 167 169 (Pubitemid 36056725)
180. C5a, a therapeutic target in sepsis. Guo RF, Ward PA, Recent Pat Antiinfect Drug Discov 2006 1 1 57 65
181. Role of C5 activation products in sepsis. Ward PA, ScientificWorldJournal 2010 10 2395 2402
182. Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. Stevens JH, O'Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA, J Clin Invest 1986 77 6 1812 1816 (Pubitemid 16062634)
183. Protective effects of C5a blockade in sepsis. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA, Nat Med 1999 5 7 788 792 (Pubitemid 29318613)
184. Protective effects of anti-C5a peptide antibodies in experimental sepsis. Huber-Lang MS, Sarma JV, McGuire SR, Lu KT, Guo RF, Padgaonkar VA, Younkin EM, Laudes IJ, Riedemann NC, Younger JG, et al. FASEB J 2001 15 3 568 570
185. Protection of innate immunity by C5aR antagonist in septic mice. Huber-Lang MS, Riedeman NC, Sarma JV, Younkin EM, McGuire SR, Laudes IJ, Lu KT, Guo RF, Neff TA, Padgaonkar VA, et al. FASEB J 2002 16 12 1567 1574 (Pubitemid 35154639)
186. Complement-induced impairment of innate immunity during sepsis. Huber-Lang MS, Younkin EM, Sarma JV, McGuire SR, Lu KT, Guo RF, Padgaonkar VA, Curnutte JT, Erickson R, Ward PA, J Immunol 2002 169 6 3223 3231 (Pubitemid 35013169)
187. Sepsis, complement and the dysregulated inflammatory response. Ward PA, Gao H, J Cell Mol Med 2009 13 10 4154 4160
188. In vivo regulation of neutrophil apoptosis by C5a during sepsis. Guo RF, Sun L, Gao H, Shi KX, Rittirsch D, Sarma VJ, Zetoune FS, Ward PA, J Leukoc Biol 2006 80 6 1575 1583 (Pubitemid 44904996)
189. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, et al. J Immunol 2001 166 11 6952 6963 (Pubitemid 32467243)
190. Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis. Guo RF, Huber-Lang M, Wang X, Sarma V, Padgaonkar VA, Craig RA, Riedemann NC, McClintock SD, Hlaing T, Shi MM, et al. J Clin Invest 2000 106 10 1271 1280
191. The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis. Flierl MA, Rittirsch D, Chen AJ, Nadeau BA, Day DE, Sarma JV, Huber-Lang MS, Ward PA, PLoS One 2008 3 7 2560
192. Apoptosis and caspases regulate death and inflammation in sepsis. Hotchkiss RS, Nicholson DW, Nat Rev Immunol 2006 6 11 813 822 (Pubitemid 44631650)
193. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction. Niederbichler AD, Hoesel LM, Westfall MV, Gao H, Ipaktchi KR, Sun L, Zetoune FS, Su GL, Arbabi S, Sarma JV, et al. J Exp Med 2006 203 1 53 61 (Pubitemid 43139645)
194. Increased C5a receptor expression in sepsis. Riedemann NC, Guo RF, Neff TA, Laudes IJ, Keller KA, Sarma VJ, Markiewski MM, Mastellos D, Strey CW, Pierson CL, et al. J Clin Invest 2002 110 1 101 108 (Pubitemid 34743470)
195. C5a receptor and thymocyte apoptosis in sepsis. Riedemann NC, Guo RF, Laudes IJ, Keller K, Sarma VJ, Padgaonkar V, Zetoune FS, Ward PA, FASEB J 2002 16 8 887 888
196. Functional roles for C5a receptors in sepsis. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Kohl J, et al. Nat Med 2008 14 5 551 557 (Pubitemid 351655216)
197. Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans. Huber-Lang M, Sarma JV, Rittirsch D, Schreiber H, Weiss M, Flierl M, Younkin E, Schneider M, Suger-Wiedeck H, Gebhard F, et al. J Immunol 2005 174 2 1104 1110 (Pubitemid 40094308)
198. Role of C5a in multiorgan failure during sepsis. Huber-Lang M, Sarma VJ, Lu KT, McGuire SR, Padgaonkar VA, Guo RF, Younkin EM, Kunkel RG, Ding J, Erickson R, et al. J Immunol 2001 166 2 1193 1199 (Pubitemid 32060279)
199. Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Laudes IJ, Chu JC, Sikranth S, Huber-Lang M, Guo RF, Riedemann N, Sarma JV, Schmaier AH, Ward PA, Am J Pathol 2002 160 5 1867 1875 (Pubitemid 34525666)
200. The role of complement, C5a and its receptors in sepsis and multiorgan dysfunction syndrome. Flierl MA, Schreiber H, Huber-Lang MS, J Invest Surg 2006 19 4 255 265 (Pubitemid 44103001)
201. Current theories on the pathophysiology of multiple organ failure after trauma. Tsukamoto T, Chanthaphavong RS, Pape HC, Injury 2010 41 1 21 26