CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin
CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin
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DOI：
10.1182/blood-2010-11-321489
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发表时间：
2011-10-13
期刊：
影响因子：
20.3
通讯作者：
Cutler, Daniel F.
中科院分区：
文献类型：
--
作者：
Doyle, Emily L.;Ridger, Victoria;Cutler, Daniel F.
内皮细胞的激活对于启动炎症反应至关重要。活化诱导韦伯-帕拉德体（WPB）与质膜融合，从而将P-选择素和VWF转移到细胞表面，在那里它们分别在白细胞和血小板的募集中起作用。长期以来，CD 63一直是WPB的一个既定组成部分，但其在炎症和止血中起作用的细胞器中存在的功能意义尚不清楚。我们发现，消融CD 63表达导致P-选择素依赖性功能的丧失：CD 63缺陷型HUVEC不能招募白细胞，CD 63缺陷型小鼠表现出白细胞滚动和招募的显着减少，我们在腹膜炎模型中表现出白细胞外渗的失败。CD 63的缺失与P-选择素本身的缺失具有相似的表型，因此CD 63是P-选择素的必需辅因子。（血。2011;118（15）：4265-4273）
The activation of endothelial cells is critical to initiating an inflammatory response. Activation induces the fusion of Weibel-Palade Bodies (WPB) with the plasma membrane, thus transferring P-selectin and VWF to the cell surface, where they act in the recruitment of leukocytes and platelets, respectively. CD63 has long been an established component of WPB, but the functional significance of its presence within an organelle that acts in inflammation and hemostasis was unknown. We find that ablating CD63 expression leads to a loss of P-selectin-dependent function: CD63-deficient HUVECs fail to recruit leukocytes, CD63-deficient mice exhibit a significant reduction in both leukocyte rolling and recruitment and we show a failure of leukocyte extravasation in a peritonitis model. Loss of CD63 has a similar phenotype to loss of P-selectin itself, thus CD63 is an essential cofactor to P-selectin. (Blood. 2011;118(15):4265-4273)