Activated platelets signal chemokine synthesis by human monocytes
Activated platelets signal chemokine synthesis by human monocytes
复制标题
DOI：
10.1172/jci118575
复制
发表时间：
1996-03-15
影响因子：
15.9
通讯作者：
Zimmerman, GA
中科院分区：
文献类型：
--
作者：
Weyrich, AS;Elstad, MR;Zimmerman, GA
人血单核细胞能够快速且长时间地粘附到显示 P-选择素的活化血小板上，P-选择素是一种识别白细胞上特定配体 P-选择素糖蛋白-1 的粘附蛋白。我们之前证明，当 P-选择素以纯化的固定形式或转染的细胞存在时，它可以调节受刺激的单核细胞的细胞因子的表达和分泌。在这里，我们发现凝血酶激活的血小板诱导单核细胞表达和分泌单核细胞趋化蛋白-1和IL-8。增强的单核因子合成需要通过血小板上的 P-选择素与白细胞上的 P-选择素糖蛋白-1 结合。然而，趋化因子的分泌并不直接由 P-选择素发出信号。相反，单核细胞的激活需要通过 P-选择素来束缚，并通过 RANTES（根据正常 T 细胞表达和推测分泌的激活进行调节）来激活，RANTES 是一种以前未知的血小板趋化因子，可在单核细胞中诱导立即早期基因产物。单核细胞粘附到活化的血小板上会导致 p65 (RelA) 的核转位，p65 是转录因子 NF-KB 家族的一个组成部分，可与单核细胞趋化蛋白 1、IL-8 和其他立即早期基因调节区的 KB 序列结合。然而，组织因子（一种在其基因的 5' 调控区也具有 KB 序列的凝血蛋白）的表达不会在粘附于活化血小板的单核细胞中被诱导。因此，单核细胞与活化血小板的接触不同地影响单核细胞产物的表达。这些实验表明，活化的血小板在体内调节炎症病变中单核细胞的趋化因子分泌，并为研究细胞间相互作用的基因调控提供了模型。
Human blood monocytes adhere rapidly and for prolonged periods to activated platelets that display P-selectin, an adhesion protein that recognizes a specific ligand on leukocytes, P-selectin glycoprotein-l. We previously demonstrated that P-selectin regulates expression and secretion of cytokines by stimulated monocytes when it is presented in a purified, immobilized form or by transfected cells. Here we show that thrombin-activated platelets induce the expression and secretion of monocyte chemotactic protein-1 and IL-8 by monocytes. Enhanced monokine synthesis requires engagement of P-selectin glycoprotein-l on the leukocyte by P-selectin on the platelet. Secretion of the chemokines is not, however, directly signaled by P-selectin; instead, tethering of the monocytes by P-selectin is required for their activation by RANTES (regulated upon activation normal T cell expressed presumed secreted), a platelet chemokine not previously known to induce immediate-early gene products in monocytes. Adhesion of monocytes to activated platelets results in nuclear translocation of p65 (RelA), a component of the NF-KB family of transcription factors that binds KB sequences in the regulatory regions of monocyte chemotactic protein-1, IL-8, and other immediate-early genes. However, expression of tissue factor, a coagulation protein that also has a KB sequence in the 5' regulatory region of its gene, is not induced in monocytes adherent to activated platelets. Thus, contact of monocytes with activated platelets differentially affects the expression of monocyte products. These experiments suggest that activated platelets regulate chemokine secretion by monocytes in inflammatory lesions in vivo and provide a model for the study of gene regulation in cell-cell interactions.