Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation
Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation
复制标题
DOI：
10.1007/s00395-007-0667-y
复制
发表时间：
2007-09-01
影响因子：
9.5
通讯作者：
Dempfle, Carl-Erik
中科院分区：
文献类型：
--
作者：
Kaelsch, Thorsten;Elmas, Elif;Dempfle, Carl-Erik
慢性炎症是动脉粥样硬化的主要促成因素，并且在患有已确定的动脉粥样硬化疾病的患者中，炎症、纤维蛋白溶解和凝血的各种标志物上调。本研究的目的是研究炎症对血小板和单核细胞活化的直接和短期影响，在健康志愿者体内内毒素血症模型中，13名平均年龄为29.5 +/- 5.4岁的健康男性受试者接受静脉注射脂多糖（LPS; 20 IU/kg IV）。在基线和LPS给药后1、2、4、6和24小时，通过全血流式细胞术测量血小板上的CD 40配体和CD 62 P表达、单核细胞上的组织因子结合和血小板-单核细胞聚集体的动力学。在相同的时间过程中，用ELISA测量可溶性CD 40-配体的血浆水平。实验性内毒素血症时血小板-单核细胞聚集、单核细胞组织因子结合和血小板表面CD 40 L表达均显著增加，并在LPS给药后1h达高峰。24小时后，所有数值均恢复至基线水平。LPS对血小板表面CD 62 P的表达和血浆sCD 40 L水平无明显影响，内毒素可激活血小板和单核细胞，上调血小板表面致动脉粥样硬化的CD 40 L。这些发现证实了体内模型中炎症通过血小板和单核细胞活化在早期动脉粥样硬化形成中的作用。
Chronic inflammation is a major contributing factor to atherosclerosis and various markers of inflammation, fibrinolysis and coagulation are upregulated in patients with established atherosclerotic disease. The aim of this study was to investigate the direct and short-term effects of inflammation on platelet and monocyte activation with an in vivo model of endotoxemia in healthy volunteers.In this study, 13 healthy male subjects with a mean age of 29.5 +/- 5.4 years received intravenous administration of lipopolysaccharide (LPS; 20 IU/kg IV). The kinetics of CD40-ligand and CD62P expression on platelets, tissue-factor binding on monocytes and platelet-monocyte aggregates were measured by whole blood flow cytometry at baseline and at 1, 2, 4, 6 and 24 hours after LPS administration. Plasma levels of soluble CD40-ligand were measured with an ELISA over the same time course. Platelet-monocyte aggregates, tissue-factor binding on monocytes and surface expression of platelet CD40L significantly increased in experimental endotoxemia in vivo, reaching peak values 1 hour after LPS administation. All values returned to baseline after 24 hours. Surface expression of CD62P on platelets and plasma levels of sCD40L did not change significantly in response to LPS.In vivo administration of endotoxin leads to an activation of platelets and monocytes with an upregulation of proatherogenic CD40L on platelets. These findings underpin the role of inflammation in early atherogenesis through platelet and monocyte activation in an in vivo model.