Medical Research Council (MRC) Laboratory for Molecular Cell Biology, University College London (UCL), London, UK.
Blood. 2011 Oct 13;118(15):4265-73. doi: 10.1182/blood-2010-11-321489. Epub 2011 Jul 29.
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.
内皮细胞的激活对于引发炎症反应至关重要。激活诱导 Weibel-Palade 小体 (WPB) 与质膜融合，从而将 P-选择素和 VWF 转移到细胞表面，在那里它们分别作用于白细胞和血小板的募集。CD63 长期以来一直是 WPB 的一个既定组成部分，但它在炎症和止血中起作用的细胞器中的存在的功能意义尚不清楚。我们发现，敲除 CD63 表达会导致 P-选择素依赖性功能丧失：CD63 缺陷的 HUVEC 无法募集白细胞，CD63 缺陷的小鼠在白细胞滚动和募集方面均显著减少，我们在腹膜炎模型中显示白细胞渗出失败。CD63 的缺失具有类似于 P-选择素本身缺失的表型，因此 CD63 是 P-选择素的必需辅助因子。
