Satta N, Toti F, Feugeas O, Bohbot A, Dachary-Prigent J, Eschwège V, Hedman H, Freyssinet J M
Thrombosis and Autoimmunity Group, Medical Faculty, Louis Pasteur University, Strasbourg, France.
J Immunol. 1994 Oct 1;153(7):3245-55.
Endotoxin-stimulated monocytes can elicit a dual procoagulant response. They express tissue factor and expose phosphatidylserine in the outer leaflet of the plasma membrane. Tissue factor, a membrane glycoprotein, is the cellular trigger of blood coagulation reactions. Phosphatidylserine is an essential anionic phospholipid for surface amplification of thrombin generation. In this study the distribution of these two procoagulant entities between activated monocytes and derived microparticles was assessed after stimulation by LPS. The presence of CD14, CD11a, and CD18, and possible associated adhesion potential were examined, particularly on microparticles. Tissue factor was evidenced by using a specific functional assay and flow cytometry. Phosphatidylserine exposure was monitored through its catalytic activity in a thrombin generation assay and by flow cytometry with the use of FITC-conjugated annexin V, a protein probe of anionic phospholipids. CD14, CD11a, and CD18 were detected by flow cytometry. The interaction of microparticle CD11a/CD18 with intracellular adhesion molecule-1 was demonstrated by using immobilized recombinant intracellular adhesion molecule-1 fusion protein. The major part of tissue factor and phosphatidylserine-dependent procoagulant activity was associated with microparticles after LPS stimulation. This was confirmed by flow cytometry. The presence of functional CD11a/CD18, and CD14 on microparticles testifies to an associated adhesion potential. These results show that membrane vesiculation could be responsible for dissemination of inducible monocyte procoagulant activities and suggest that derived microparticles could also participate in endothelium stimulation. This emphasizes the role of monocyte as a central element in the coupling between inflammation/infection and thrombosis.
内毒素刺激的单核细胞可引发双重促凝反应。它们表达组织因子并使磷脂酰丝氨酸暴露于质膜外小叶。组织因子是一种膜糖蛋白,是血液凝固反应的细胞触发因子。磷脂酰丝氨酸是凝血酶生成表面放大的必需阴离子磷脂。在本研究中,评估了脂多糖刺激后这两种促凝物质在活化单核细胞和衍生微粒之间的分布。检测了CD14、CD11a和CD18的存在以及可能相关的黏附潜能,特别是在微粒上。通过特异性功能测定和流式细胞术证实了组织因子的存在。通过凝血酶生成测定中的催化活性以及使用FITC偶联的膜联蛋白V(一种阴离子磷脂的蛋白质探针)的流式细胞术监测磷脂酰丝氨酸的暴露。通过流式细胞术检测CD14、CD11a和CD18。使用固定化重组细胞间黏附分子-1融合蛋白证明了微粒CD11a/CD18与细胞间黏附分子-1的相互作用。脂多糖刺激后,组织因子和磷脂酰丝氨酸依赖性促凝活性的主要部分与微粒相关。这通过流式细胞术得到证实。微粒上功能性CD11a/CD18和CD14的存在证明了相关的黏附潜能。这些结果表明膜囊泡形成可能是诱导性单核细胞促凝活性传播的原因,并表明衍生微粒也可能参与内皮刺激。这强调了单核细胞作为炎症/感染与血栓形成之间耦合的核心要素的作用。