The endothelium as physiological source of properdin: role of wall shear stress
The endothelium as physiological source of properdin: role of wall shear stress
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DOI：
10.1016/s0161-5890(02)00215-8
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发表时间：
2003-01-01
影响因子：
3.6
通讯作者：
Zakrzewicz, A
中科院分区：
文献类型：
--
作者：
Bongrazio, M;Pries, AR;Zakrzewicz, A
备解素是补体激活的另一种途径的正向调节因子。它可以由外周血细胞释放，但不能在肝脏合成，血浆中备解素的生理来源尚不清楚。内皮细胞是几种补体成分的肝外来源，剪切力可以调节它们的表达。本研究的目的是分析切应力暴露的内皮细胞(EC)作为血浆特性的生理来源。利用锥板装置将人脐静脉内皮细胞(HUVEC)和人心脏微血管内皮细胞(HCMEC)暴露于切应力中，并用RT-PCR、Northern和Western印迹分析相应蛋白的表达。在未经处理的EC中几乎检测不到备解素的mRNA，但在层流切应力暴露(6dyn/cm(2)；24小时)下强烈诱导。备解素也在蛋白质水平上被诱导，并在细胞外隔室释放。备解素上调需要2-3dyn/cm的剪应力(2)不是瞬时的，并且通过恢复静态条件是可逆的。湍流暴露可导致比层流暴露高两倍的备解素的诱导。内皮细胞在剪切力作用下合成备解素的能力表明内皮细胞是血浆备解素的生理来源，并提示流动条件与替代途径的调节之间存在联系。此外，湍流诱导的较强的备解素可能参与了动脉粥样硬化的病理过程。(C)2003爱思唯尔科学有限公司。保留所有权利。
Properdin is a positive regulator of the alternative pathway of complement activation. It can be released by peripheral blood cells but is not synthesized in the liver and the physiological source of properdin in plasma is unknown. The endothelium is an extra-hepatic source for several complement components and shear stress can modulate their expression. The aim of this study was to analyze shear stress-exposed endothelial cells (EC) as physiological source for plasma properdin.Human umbilical vein EC (HUVEC) and human cardiac microvascular EC (HCMEC) were exposed to shear stress using a cone-and-plate apparatus and properdin expression was analyzed by RT-PCR, Northern, and Western blot. mRNA for properdin is barely detectable in untreated EC but strongly induced by laminar shear stress exposure (6 dyn/cm(2); 24 h). Properdin is induced also at the protein level and is released in the extracellular compartment. Properdin up-regulation requires a shear stress of 2-3 dyn/cm(2) is not transient, and is reversible by restoration of static conditions. Turbulent flow exposure results in two times higher induction of properdin than laminar flow exposure.The ability of endothelial cells exposed to shear stress to synthesize properdin proposes the endothelium as physiological source for plasma properdin and suggests a link between flow conditions and the modulation of the alternative pathway. Furthermore, the stronger properdin induction by turbulent flow may suggest an involvement in the pathology of atherosclerosis. (C) 2003 Elsevier Science Ltd. All rights reserved.