von Willebrand factor promotes leukocyte extravasation
von Willebrand factor promotes leukocyte extravasation
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DOI：
10.1182/blood-2010-03-276311
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发表时间：
2010-11-25
期刊：
影响因子：
20.3
通讯作者：
Vestweber, Dietmar
中科院分区：
文献类型：
--
作者：
Petri, Bjoern;Broermann, Andre;Vestweber, Dietmar
血管性血友病因子 (VWF) 在止血过程中发挥着重要作用，但也被认为会促进炎症过程。 VWF 的基因消融同时导致 P-选择素表达缺陷，从而难以识别 VWF 特异性功能。因此，我们分析了针对 VWF 的阻断抗体是否能够干扰中性粒细胞外渗。我们发现这些抗体抑制中性粒细胞募集到硫代乙醇酸发炎的腹膜和 KC 刺激的提睾肌中约 50%。虽然不涉及血小板 VWF，但 VWF 对粒细胞募集的贡献严格取决于血小板的存在及其 VWF 受体糖蛋白 Ib 的可及性。令人惊讶的是，血小板 P-选择素对于白细胞外渗来说在很大程度上是可有可无的，这与我们的观察结果一致，即抗 VWF 抗体不影响白细胞滚动和粘附。在寻找白细胞捕获下游可能的影响时，我们发现抗 VWF 抗体显着抑制巯基乙酸盐诱导的血管通透性。通透性的增加与循环粒细胞无关，表明它不是中性粒细胞血渗的副作用。总的来说，我们的结果表明，VWF 相关血小板在白细胞与血管壁对接的下游步骤中强烈支持中性粒细胞外渗。该步骤可能与内皮屏障不稳定促进的白细胞渗出有关。 （血。2010；116（22）：4712-4719）
von Willebrand factor (VWF) is an important player in hemostasis but has also been suggested to promote inflammatory processes. Gene ablation of VWF causes a simultaneous defect in P-selectin expression making it difficult to identify VWF-specific functions. Therefore, we analyzed whether blocking antibodies against VWF would be able to interfere with neutrophil extravasation. We found that these antibodies inhibited neutrophil recruitment into thioglycollate-inflamed peritoneum and KC-stimulated cremaster by approximately 50%. Whereas platelet-VWF was not involved, the contribution of VWF to granulocyte recruitment was strictly dependent on the presence of platelets and the accessibility of their VWF-receptor glycoprotein Ib. Surprisingly, platelet P-selectin was largely dispensable for leukocyte extravasation, in agreement with our observation that anti-VWF antibodies did not affect leukocyte rolling and adhesion. Searching for possible effects downstream of leukocyte capture, we found that anti-VWF antibodies significantly inhibited thioglycollate-induced vascular permeability. The in-crease of permeability was independent of circulating granulocytes, showing that it was not a side effect of neutrophil diapedesis. Collectively, our results demonstrate that VWF-associated platelets strongly support neutrophil extravasation at a step downstream of leukocyte docking to the vessel wall. This step could be related to leukocyte diapedesis facilitated by destabilization of the endothelial barrier. (Blood. 2010; 116(22): 4712-4719)