Biological activities of C1 inhibitor.
Biological activities of C1 inhibitor.
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DOI：
10.1016/j.molimm.2008.06.028
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发表时间：
2008-10
影响因子：
3.6
通讯作者：
Lu, Fengxin
中科院分区：
文献类型：
--
作者：
Davis, Alvin E., III;Mejia, Pedro;Lu, Fengxin
关键词：
从广义上讲，C1抑制剂在调节血管通透性和抑制炎症方面发挥着重要作用。血管通透性控制主要是通过抑制两种参与缓激肽生成的蛋白酶、因子 XIIa 和血浆激肽释放酶（血浆激肽释放酶-激肽系统）来实现。然而，抗炎功能是通过多种活性发挥的，包括抑制补体系统蛋白酶（C1r、C1s、MASP2）和血浆激肽释放酶-激肽系统蛋白酶，以及与许多不同蛋白质、细胞和感染因子的相互作用。这些最近描述的、尚未完全表征的活性具有多种潜在功能，包括在炎症部位浓缩 C1 抑制剂、抑制替代补体途径激活、抑制革兰氏阴性内毒素的生物活性、增强细菌吞噬和杀灭作用，以及抑制白细胞流入炎症部位。 C1 抑制剂已被证明可用于治疗多种炎症性疾病动物模型，包括革兰氏阴性细菌败血症和内毒素休克、抑制超急性移植排斥以及治疗多种缺血再灌注损伤（心脏、肠道、骨骼肌、肝脏、大脑）。在人类中，早期数据在心肌再灌注损伤方面似乎特别有希望。 C1 抑制剂在这些情况下的作用机制尚不完全清楚，但除了不涉及蛋白酶抑制的其他 C1 抑制剂活性的可变贡献外，还涉及补体和接触系统激活的抑制。
Broadly speaking, C1 inhibitor plays important roles in the regulation of vascular permeability and in the suppression of inflammation. Vascular permeability control is exerted largely through inhibition of two of the proteases involved in the generation of bradykinin, factor XIIa and plasma kallikrein (the plasma kallikrein-kinin system). Anti-inflammatory functions, however, are exerted via several activities including inhibition of complement system proteases (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases, in addition to interactions with a number of different proteins, cells and infectious agents. These more recently described, as yet incompletely characterized, activities serve several potential functions, including concentration of C1 inhibitor at sites of inflammation, inhibition of alternative complement pathway activation, inhibition of the biologic activities of gram negative endotoxin, enhancement of bacterial phagocytosis and killing, and suppression of the influx of leukocytes into a site of inflammation. C1 inhibitor has been shown to be therapeutically useful in a variety of animal models of inflammatory diseases, including gram negative bacterial sepsis and endotoxin shock, suppression of hyperacute transplant rejection, and treatment of a variety of ischemia-reperfusion injuries (heart, intestine, skeletal muscle, liver, brain). In humans, early data appear particularly promising in myocardial reperfusion injury. The mechanism (or mechanisms) of the effect of C1 inhibitor in these conditions is (are) not completely clear, but involve inhibition of complement and contact system activation, in addition to variable contributions from other C1 inhibitor activities that do not involve protease inhibition.
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影响因子：
4.4
作者：
Cai, SH;Dole, VS;Davis, AE
通讯作者：
Davis, AE
影响因子：
3
作者：
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DOI：
10.1016/j.bbrc.2006.09.023
发表时间：
2006-11-10
影响因子：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
LEFER, AM