Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63
Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63
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DOI：
10.1038/ncomms4738
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发表时间：
2014-04-01
影响因子：
16.6
通讯作者：
Rescher, Ursula
中科院分区：
文献类型：
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作者：
Poeter, Michaela;Brandherm, Ines;Rescher, Ursula
为了使白细胞粘附于活化的内皮，白细胞受体p -选择素从韦贝尔-帕拉德体（WPB）释放到内皮细胞表面，在那里它被CD63稳定。在这里，我们报道了人脐静脉内皮细胞（HUVEC）中膜联蛋白A8 （anxA8）的缺失强烈地减少了CD63和p -选择素的细胞表面呈现，同时白细胞滚动和粘附减少。我们证实了炎症激活的内皮小静脉中白细胞粘附性受损的anxa8缺陷小鼠。我们发现，缺乏anxa8的HUVEC的WPB中含有较少的CD63，这是由于CD63从晚期多泡内体转运到WPB的不当引起的，CD63保留在腔内小泡中。因此，WPB胞吐后CD63细胞表面水平降低，导致p -选择素再内化增强。我们的数据支持一个模型，在这个模型中，anxA8通过向WPB提供足量的p选择素调节因子CD63，影响白细胞向活化的内皮细胞募集。
To enable leukocyte adhesion to activated endothelium, the leukocyte receptor P-selectin is released from Weibel-Palade bodies (WPB) to the endothelial cell surface where it is stabilized by CD63. Here we report that loss of annexin A8 ( anxA8) in human umbilical vein endothelial cells (HUVEC) strongly decreases cell surface presentation of CD63 and P-selectin, with a concomitant reduction in leukocyte rolling and adhesion. We confirm the compromised leukocyte adhesiveness in inflammatory-activated endothelial venules of anxA8-deficient mice. We find that WPB of anxA8-deficient HUVEC contain less CD63, and that this is caused by improper transport of CD63 from late multivesicular endosomes to WPB, with CD63 being retained in intraluminal vesicles. Consequently, reduced CD63 cell surface levels are seen following WPB exocytosis, resulting in enhanced P-selectin re-internalization. Our data support a model in which anxA8 affects leukocyte recruitment to activated endothelial cells by supplying WPB with sufficient amounts of the P-selectin regulator CD63.