GLYCOPROTEIN-IV MEDIATES THROMBOSPONDIN-DEPENDENT PLATELET-MONOCYTE AND PLATELET-U937 CELL-ADHESION
GLYCOPROTEIN-IV MEDIATES THROMBOSPONDIN-DEPENDENT PLATELET-MONOCYTE AND PLATELET-U937 CELL-ADHESION
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DOI：
10.1172/jci114197
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发表时间：
1989-08-01
影响因子：
15.9
通讯作者：
NACHMAN, RL
中科院分区：
文献类型：
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作者：
SILVERSTEIN, RL;ASCH, AS;NACHMAN, RL
活化血小板和单核吞噬细胞之间的粘附相互作用可能有助于这些细胞在调节炎症、血栓形成和动脉粥样硬化中发挥作用。我们以前已经表明，这种粘附相互作用是由活化血小板表面糖蛋白血小板反应蛋白（TSP）的表达介导的。我们现在表明，TSP依赖性血小板单核细胞相互作用介导的糖蛋白IV（GPIV），一种内在的膜蛋白，最近被确定为细胞表面TSP受体。通过流式细胞术评估，GPIV的单克隆抗体与人单核细胞系U937的细胞结合，并抑制83%的125 I-TSP与细胞表面的结合。用抗GPIV预孵育的U937细胞未被凝血酶刺激的血小板玫瑰花化（与对照抗单核细胞抗体相比，抑制率为72%）。此外，当在饱和浓度的抗GPIV单克隆抗体存在下刺激血小板时，只有18%的U937细胞出现玫瑰色（78%抑制）。包括抗GPIb的对照抗体不抑制玫瑰花结形成。这些数据表明，TSP可以通过与血小板和单核细胞表面上的GPIV相互作用而交叉排列。这种分子桥可以在各种病理生理环境中介导血小板-巨噬细胞通讯。
An adhesive interaction between activated platelets and mononuclear phagocytes may contribute to the role these cells play in regulating inflammation, thrombosis, and atherosclerosis. We have previously shown that this adhesive interaction is mediated by the expression of the glycoprotein thrombospondin (TSP) on the surface of activated platelets. We now show that TSP-dependent platelet-monoycte interactions are mediated by glycoprotein IV (GPIV), an intrinsic membrane protein recently identified as a cell surface TSP receptor. Monoclonal antibodies to GPIV bound to cells of the human monocytoid line U937 as assessed by flow cytometry and inhibited the binding of 125I-TSP to the cell surface by 83%. U937 cells preincubated with anti-GPIV were not rosetted by thrombin-stimulated platelets (72% inhibition compared with control anti-monocyte antibodies). In addition, when platelets were stimulated in the presence of saturating concentrations of monoclonal antibodies to GPIV, only 18% of U937 cells were rosetted (78% inhibition). Control antibodies including anti-GPIb did not inhibit rosette formation. These data suggest that TSP can cross-line platelets and monocytes via an interaction with GPIV on the surface of both cells. This molecular bridge may mediate platelet-macrophage communication in various pathophysiologic settings.