Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis.
Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis.
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DOI：
10.1007/978-1-4614-0106-3_9
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发表时间：
2012
影响因子：
--
通讯作者：
Ward, Peter A.
中科院分区：
文献类型：
--
作者：
Bosmann, Markus;Ward, Peter A.
补体系统在先天免疫防御感染因子中起着重要作用，但过度激活补体可导致严重的组织损伤。补体的全身性（血管内）激活可通过C5a导致中性粒细胞（PMN）活化、封存和粘附于肺毛细血管内皮，导致血管内皮细胞损伤和坏死和急性肺损伤（ALI）。肺内（肺泡内）补体激活可引起补体和pmn依赖的ALI，导致细胞因子/趋化因子风暴，导致强烈的ALI。令人惊讶的是，由于凝血酶的作用，C3−/−小鼠以C5a依赖的方式发展出全强度的ALI，凝血酶直接从C5产生C5a。关于第二种C5a受体C5L2在ALI发展中的作用，有相互矛盾的证据。越来越多的证据表明，C5a可能抑制炎症反应或将炎症反应从Th1转移到Th2，从而影响先天免疫系统。最后，在实验性多微生物脓毒症中，有证据表明，许多不良后果可能与C5a的作用及其两种受体C5aR和C5L2的参与有关。这些观察结果强调了C5a在各种炎症环境中作用的多样性。
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.
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DOI：
10.4049/jimmunol.0903678
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Amara U;Flierl MA;Rittirsch D;Klos A;Chen H;Acker B;Brückner UB;Nilsson B;Gebhard F;Lambris JD;Huber-Lang M
通讯作者：
Huber-Lang M
影响因子：
82.9
作者：
Donnelly, SC;Haslett, C;Bucala, R
通讯作者：
Bucala, R
影响因子：
30.5
作者：
Karp, CL;Grupe, A;Wills-Karp, M
通讯作者：
Wills-Karp, M
影响因子：
6
作者：
Laudes, IJ;Chu, JC;Ward, PA
通讯作者：
Ward, PA
影响因子：
15.9
作者：
Köhl, J;Baelder, R;Wills-Karp, M
通讯作者：
Wills-Karp, M