Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex
Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex
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DOI：
10.4049/jimmunol.173.11.6921
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Tedesco, F
中科院分区：
文献类型：
--
作者：
Bossi, F;Fischetti, F;Tedesco, F
感染性休克在患有脑膜炎球菌病的终末补体成分遗传缺陷的患者中很少发生，这使我们怀疑终末补体复合物参与血管渗漏。为此，在Transwell系统中测试了无细胞溶解活性的可溶性末端补体复合物（SC 5 b-9）的透化作用，测量了通过单层内皮细胞泄漏的荧光素标记的BSA（FITC-BSA）的量。复合物引起的增加渗透性FITC-BSA 15分钟后，而不是迅速响应缓激肽（BK）。SC 5 b-9的作用被HOE-140或CV-3988（分别为BK B2和血小板活化因子受体的两种选择性拮抗剂）部分降低，并被两种拮抗剂的混合物完全中和。另外，激肽释放酶的特异性抑制剂DX-88部分抑制了SC 56 -9的活性。内皮细胞与SC 5 b-9孵育30分钟后释放的透化因子导致白蛋白（如BK）迅速渗漏。活体显微镜检查证实了局部应用SC 5 b-9后15分钟循环FITC-BSA通过肠系膜微血管外渗以及HOE-140和CV-3988混合物的完全中和。SC 5 b-9诱导肠系膜内皮细胞内皮细胞间连接的开放，通过透射电子显微镜记录。
The infrequent occurrence of septic shock in patients with inherited deficiencies of the terminal complement components experiencing meningococcal disease led us to suspect that the terminal complement complex is involved in vascular leakage. To this end, the permeabilizing effect of the cytolytically inactive soluble terminal complement complex (SC5b-9) was tested in a Transwell system measuring the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of endothelial cells. The complex caused increased permeability to FITC-BSA after 15 min as opposed to the prompt response to bradykinin (BK). The effect of SC5b-9 was partially reduced by HOE-140 or CV-3988, two selective antagonists of BK B2 and platelet-activating factor receptors, respectively, and was completely neutralized by the mixture of the two antagonists. Also, DX-88, a specific inhibitor of kallikrein, partially inhibited the activity of SC56-9. The permeabilizing factor(s) released after 30 min of incubation of endothelial cells with SC5b-9 caused a prompt leakage of albumin like BK. Intravital microscopy confirmed both the extravasation of circulating FITC-BSA across mesenteric microvessels 15 min after topical application of SC5b-9 and the complete neutralization by the mixture of HOE-140 and CV-3988. SC5b-9 induced opening of interendothelial junctions in mesenteric endothelium documented by transmission electron microscopy.