Mechanotransduction in leukocyte activation: a review.
Mechanotransduction in leukocyte activation: a review.
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发表时间：
2007
期刊：
影响因子：
1.1
通讯作者：
A. Makino;H. Shin;Y. Komai;S. Fukuda;M. Coughlin;M. Sugihara-Seki;G. Schmid-Schönbein
中科院分区：
文献类型：
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作者：
A. Makino;H. Shin;Y. Komai;S. Fukuda;M. Coughlin;M. Sugihara-Seki;G. Schmid-Schönbein
我们回顾了最近的证据，这些证据表明循环和组织中的白细胞可以很容易地对大约1到10dyn/cm2范围内的流体剪应力的生理水平做出反应，这个范围低于实现显著的被动粘弹性反应的水平。激活的中性粒细胞对流体剪切的反应包括片状脂膜的快速回缩和整合素结合部位的膜分离。相反，暴露在流体剪应力下的未激活的中性粒细胞亚群可能会投射假足。证据表明，G蛋白偶联受体通过流体剪切下调，伴随着RAC相关小GTP酶的下调和F-肌动蛋白的解聚，有助于收缩片状脂膜，并与β2整合素的蛋白水解性切割一起促进膜分离。此外，还存在一种上调和下调流体剪切反应的机制，该机制涉及一氧化氮和第二信使环鸟苷一磷酸(CGMP)。循环中白细胞的许多生理活动都受到流体剪切力的影响，包括淋巴细胞的跨内皮迁移。我们描述了一种慢性高血压的疾病模型，其流体剪切反应减弱，对微血管血流有深远的影响。
We review recent evidence which suggests that leukocytes in the circulation and in the tissue may readily respond to physiological levels of fluid shear stress in the range between about 1 and 10 dyn/cm 2, a range that is below the level to achieve a significant passive, viscoelastic response. The response of activated neutrophilic leukocytes to fluid shear consists of a rapid retraction of lamellipodia with membrane detachment from integrin binding sites. In contrast, a subgroup of non-activated neutrophils may project pseudopods after exposure to fluid shear stress. The evidence suggests that G-protein coupled receptor downregulation by fluid shear with concomitant downregulation of Rac-related small GTPases and depolymerization of F-actin serves to retract the lamellipodia in conjunction with proteolytic cleavage of beta 2 integrin to facilitate membrane detachment. Furthermore, there exists a mechanism to up- and down-regulate the fluid shear-response, which involves nitric oxide and the second messenger cyclic guanosine monophosphate (cGMP). Many physiological activities of circulating leukocytes are under the influence of fluid shear stress, including transendothelial migration of lymphocytes. We describe a disease model with chronic hypertension that suffers from an attenuated fluid shear-response with far reaching implications for microvascular blood flow.