A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process
A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process
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DOI：
10.1182/blood.v91.8.3028.3028_3028_3036
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发表时间：
1998-04-15
期刊：
影响因子：
20.3
通讯作者：
Kubes, P
中科院分区：
文献类型：
--
作者：
Ostrovsky, L;King, AJ;Kubes, P
本研究的目的是确定中性粒细胞与固定的血小板黏附的分子机制，特别关注中性粒细胞与血小板相互作用的旁分泌系统的可能存在。将血小板固定在I型胶原包被的盖片上，放置在流室中，中性粒细胞以1~4dynes/cm(2)的剪应力在这些融合的单层中灌流。中性粒细胞滚动，相当大比例(25%至50%)附着在血小板单层上。P-选择素在血小板表面大量表达，并介导所有的滚动，而β(2)-整合素则介导牢固的黏附。黏附的激活机制是必要的，因为固定的中性粒细胞继续在固定的血小板上滚动，但不黏附。与胶原黏附的血小板产生显著水平的血小板激活因子(PAF)。因此，PAF受体拮抗剂(WEB 2086)显著抑制中性粒细胞与血小板的牢固黏附。仅用乙酰水解酶处理血小板，可将膜相关PAF转化为Lyso PAF，可防止60%的黏附。这些数据表明，血小板表面的PAF介导了很大一部分黏附相互作用。将一些选择素结合的碳水化合物(岩藻糖胶或可溶性SLeX类似物，但不是葡聚糖硫酸盐)添加到血小板中，导致滚动的中性粒细胞立即粘连，这一事件在组胺或凝血酶处理的内皮细胞或P-选择素转染体中没有观察到。这些数据支持这样的观点，即中性粒细胞的固定化血小板上存在旁分泌激活过程。这一过程可以在血小板上得到极大的增强，并可能涉及到通过P-选择素的信号机制。(C)1998年由美国血液病学会主办。
The aim of this study was to identify the molecular mechanisms involved in neutrophil adhesion to immobilized platelets with particular focus on the possible existence of a juxtacrine system for neutrophil-platelet interactions. Platelets were immobilized onto collagen (type I)-coated coverslips that were placed in a flow chamber and neutrophils were perfused across these confluent monolayers at a shear stress of 1 to 4 dynes/cm(2). Neutrophils rolled, and a significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin was expressed in very large quantities on the surface of platelets and mediated all of the rolling, whereas the beta(2)-integrin mediated firm adhesion. An activation mechanism for adhesion was necessary inasmuch as fixed neutrophils continued to roll on immobilized platelets, but did not adhere. Platelets adherent to collagen produced significant levels of platelet-activating factor (PAF). Accordingly, the firm adhesion of neutrophils to platelets was significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of only the platelets with acetylhydrolase, which converts membrane-associated PAF to lyso PAF, prevented 60% of the adhesion. These data suggest that PAF, on the surface of platelets, mediated a significant portion of the adhesive interaction. Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs but not dextran sulfate) to the platelets caused rolling neutrophils to immediately adhere, an event that was not observed on histamine or thrombin-treated endothelium or P-selectin transfectants. These data support the view that a juxtacrine activation process exists on immobilized platelets for neutrophils. This process can be greatly enhanced on platelets and may involve a signaling mechanism through P-selectin. (C) 1998 by The American Society of Hematology.