血管性血友病因子
血小板
止血
免疫学
糖蛋白Ib
炎症
促炎细胞因子
血小板膜糖蛋白
受体
血小板活化
医学
败血症
血小板糖蛋白GPIb-IX复合物
内科学
作者
Adam Corken,Susan Russell,Judith A. Dent,Steven R. Post,Jerry Ware
标识
DOI:10.1161/atvbaha.113.303113
摘要
Objective— The platelet glycoprotein Ib-IX (GP Ib-IX) receptor is a well-characterized adhesion receptor supporting hemostasis and thrombosis via interactions with von Willebrand factor. We examine the GP Ib-IX/von Willebrand factor axis in murine polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP). Approach and Results— Genetic absence of the GP Ib-IX ligand, von Willebrand factor, prolongs survival after CLP, but absence of the receptor, GP Ib-IX, does not. Because absence of either von Willebrand factor or GP Ib-IX significantly impairs hemostasis and thrombosis, we sought to define additional GP Ib-IX–dependent pathways impacting survival in the CLP model. We document that the absence of GP Ib-IX leads to reduced platelet–neutrophil and platelet–monocyte interactions. Twenty-four hours after CLP, absence of GP Ib-IX coincides with an alteration in cytokine levels, such as tumor necrosis factor-α secreted by monocytes, and increased macrophage-1 antigen expression by neutrophils. Conclusions— In contrast to the well-characterized proinflammatory properties of platelets, we describe in the CLP model an anti-inflammatory property associated with platelet GP Ib-IX. Thus, a single platelet receptor displays a dual modulatory role in both the thrombotic and inflammatory pathways associated with polymicrobial sepsis. In sharing leucine-rich motifs with toll-like receptors, platelet GP Ib-IX can be considered a multifunctional participant in hemostasis, thrombosis, and the inflammatory cascade. The results highlight a dynamic role for platelets in systemic inflammation and add to the complex pathophysiologic events that occur during the dysregulated coagulation and inflammation associated with sepsis.
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