Crosstalk between the coagulation and complement systems in sepsis.
Crosstalk between the coagulation and complement systems in sepsis.
复制标题
DOI：
10.1016/j.thromres.2014.03.014
复制
发表时间：
2014-05
影响因子：
7.5
通讯作者：
Coggeshall KM
中科院分区：
文献类型：
--
作者：
Lupu F;Keshari RS;Lambris JD;Coggeshall KM
脓毒症是止血和补体系统的有效激活剂。虽然这些蛋白水解级联的局部激活有助于宿主防御，但它们不受控制的全身激活具有导致多器官衰竭和死亡的主要组织损伤作用。我们已经广泛研究了实验性脓毒症中补体和凝血级联的激活，使用活细菌（如革兰氏阴性大肠杆菌或革兰氏阳性金黄色葡萄球菌和炭疽杆菌）或细菌产物肽聚糖激发狒狒。我们观察到，这些挑战迅速诱导弥散性血管内凝血和强大的补体激活。我们应用了一种有效的C3转化酶抑制剂，坎普他汀，它可以防止脓毒症诱导的补体激活，减少血小板减少，减少凝血反应，并保留内皮抗凝特性。总的来说，我们的工作表明，活细菌和细菌产物激活补体和凝血级联反应，并且阻断补体激活产物的形成，特别是在严重脓毒症的器官衰竭阶段，可能是一种潜在的重要治疗策略。
Sepsis is a potent activator of the hemostatic and complement systems. While local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects that lead to multiple organ failure and death. We have extensively studied the activation of complement and coagulation cascades in experimental sepsis using baboons challenged with live bacteria, such as Gram-negative Escherichia coli or Gram-positive Staphylococcus aureus and Bacillus anthracis, or with the bacterial product peptidoglycan. We observed that these challenges rapidly induce disseminated intravascular coagulation and robust complement activation. We applied a potent C3 convertase inhibitor, compstatin, which prevented sepsis-induced complement activation, reduced thrombocytopenia, decreased the coagulopathic responses, and preserving the endothelial anticoagulant properties. Overall, our work demonstrates that live bacteria and bacterial products activate the complement and coagulation cascades, and that blocking formation of complement activation products, especially during the organ failure stage of severe sepsis could be a potentially important therapeutic strategy.
登录
查看更多内容
影响因子：
3.6
作者：
Schuerholz, T;Leuwer, M;Marx, G
通讯作者：
Marx, G
DOI：
10.1165/rcmb.2013-0219oc
发表时间：
2014-02-01
影响因子：
6.4
作者：
Keshari, Ravi S.;Silasi-Mansat, Robert;Lupu, Florea
通讯作者：
Lupu, Florea
影响因子：
82.9
作者：
Huber-Lang, Markus;Sarma, J. Vidya;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
3.6
作者：
Davis, Alvin E., III;Mejia, Pedro;Lu, Fengxin
通讯作者：
Lu, Fengxin
影响因子：
15.9
作者：
GHEBREHIWET, B;RANDAZZO, BP;KAPLAN, AP
通讯作者：
KAPLAN, AP