title: Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis.
abstract: The complement system plays a major role in innate immune defenses against infectious agents, but exaggerated activation of complement can lead to severe tissue injury. Systemic (intravascular) activation of complement can, via C5a, lead to neutrophil (PMN) activation, sequestration and adhesion to the pulmonary capillary endothelium, resulting in damage and necrosis of vascular endothelial cells and acute lung injury (ALI). Intrapulmonary (intraalveolar) activation of complement can cause ALI that is complement and PMN-dependent, resulting in a cytokine/chemokine storm that leads to intense ALI. Surprisingly, C3(-/-) mice develop the full intensity of ALI in a C5a-dependent manner due to the action of thrombin that generates C5a directly from C5. There is conflicting evidence on the role of the second C5a receptor, C5L2 in development of ALI. There is accumulating evidence that C5a may suppress inflammatory responses or divert them from Th1 to Th2 responses, impacting the innate immune system. Finally, in experimental polymicrobial sepsis, there is evidence that many of the adverse outcomes can be linked to the roles of C5a and engagement of its two receptors, C5aR and C5L2. These observations underscore the diversity of effects of C5a in a variety of inflammatory settings.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-5602, USA. markusb@umich.edu
authors.forename: Markus
authors.initials: M
authors.lastname: Bosmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology*; D000706:Anaphylatoxins / Q000276:immunology*; D000818:Animals; D003176:Complement C3 / Q000276:immunology*; D003182:Complement C5 / Q000276:immunology*; D006801:Humans; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology; D018805:Sepsis / Q000276:immunology*
chemical_list: D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor