Department of Surgery, Malmö University Hospital, Malmö, Sweden.
Platelets. 2009 Nov;20(7):505-12. doi: 10.3109/09537100903215417.
Platelets contribute to blood coagulation at sites of vascular injury and to the recruitment of leukocytes at sites of inflammation. Under pathological conditions, platelets are involved in numerous diseases and clinical complications, such as deep venous thrombosis, embolism and atherosclerosis. But so far, little is known about the mechanisms of inflammation in large veins and the role of platelets in inflamed large veins. For this purpose, we investigated primary and secondary interactions between platelets, leukocytes and endothelial cells in the femoral vein in vivo with special regard to the role of CD62P (P-selectin) and CD162 (PSGL-1). Mice were challenged with lipopolysaccharide (LPS)/D-galactosamine (D-gal) and either CD162 or CD62P was blocked by intravenous administration of a corresponding antibody at the time point of LPS/D-gal injection. Four hours after LPS/gal injection, intravital fluorescence microscopy of the femoral vein was performed and primary and secondary platelet-leukocyte-endothelial cell-interactions were visualized after in vivo platelet and leukocyte staining with rhodamine 6G. Analysis of intravital fluorescence microscopy revealed that LPS/D-gal caused a strong inflammatory reaction of the venous endothelium with significant induction of platelet and leukocyte tethering, rolling and adhesion. Secondary interactions of platelets to adherent or rolling platelets or leukocytes were also increased after LPS/D-gal-injection. Immunoneutralization of either CD162 or CD62P significantly decreased platelet primary and secondary capture as well as leukocyte rolling and adhesion. CD162 and CD62P play a central role in mediating inflammatory primary and secondary interactions of platelets and leukocytes to the endothelium in inflamed large veins in vivo. Thus, blocking CD162 or CD62P might be an attractive tool for preventing platelet and leukocyte-driven venous diseases.
血小板在血管损伤部位促进血液凝固，并在炎症部位募集白细胞。在病理条件下，血小板参与多种疾病和临床并发症，如深静脉血栓形成、栓塞和动脉粥样硬化。但到目前为止，人们对大静脉炎症的机制以及血小板在炎症大静脉中的作用知之甚少。为此，我们研究了体内股静脉中血小板、白细胞和内皮细胞之间的原发性和继发性相互作用，特别关注 CD62P（P-选择素）和 CD162（PSGL-1）的作用。在 LPS/D-gal 注射时，通过静脉内给予相应的抗体，用 LPS/D-gal 挑战小鼠，并阻断 CD162 或 CD62P。在 LPS/D-gal 注射后 4 小时，对股静脉进行活体荧光显微镜检查，并在体内用 rhodamine 6G 对血小板和白细胞进行染色，观察原发性和继发性血小板-白细胞-内皮细胞相互作用。活体荧光显微镜分析显示，LPS/D-gal 引起静脉内皮的强烈炎症反应，导致血小板和白细胞的栓系、滚动和黏附显著增加。LPS/D-gal 注射后，血小板与黏附或滚动的血小板或白细胞的继发性相互作用也增加。免疫中和 CD162 或 CD62P 可显著减少血小板原发性和继发性捕获以及白细胞滚动和黏附。CD162 和 CD62P 在介导血小板和白细胞与体内炎症大静脉内皮的炎症原发性和继发性相互作用中起核心作用。因此，阻断 CD162 或 CD62P 可能是预防血小板和白细胞驱动的静脉疾病的有吸引力的工具。
