Clemetson K J, Clemetson J M, Proudfoot A E, Power C A, Baggiolini M, Wells T N
Theodor Kocher Institute, University of Berne, Berne, Switzerland; and Serono Pharmaceutical Research Institute SA, Geneva, Switzerland.
Blood. 2000 Dec 15;96(13):4046-54.
Platelets are known to contain platelet factor 4 and beta-thromboglobulin, alpha-chemokines containing the CXC motif, but recent studies extended the range to the beta-family characterized by the CC motif, including RANTES and Gro-alpha. There is also evidence for expression of chemokine receptors CCR4 and CXCR4 in platelets. This study shows that platelets have functional CCR1, CCR3, CCR4, and CXCR4 chemokine receptors. Polymerase chain reaction detected chemokine receptor messenger RNA in platelet RNA. CCR1, CCR3, and especially CCR4 gave strong signals; CXCR1 and CXCR4 were weakly positive. Flow cytometry with specific antibodies showed the presence of a clear signal for CXCR4 and weak signals for CCR1 and CCR3, whereas CXCR1, CXCR2, CXCR3, and CCR5 were all negative. Immunoprecipitation and Western blotting with polyclonal antibodies to cytoplasmic peptides clearly showed the presence of CCR1 and CCR4 in platelets in amounts comparable to monocytes and CCR4 transfected cells, respectively. Chemokines specific for these receptors, including monocyte chemotactic protein 1, macrophage inflammatory peptide 1alpha, eotaxin, RANTES, TARC, macrophage-derived chemokine, and stromal cell-derived factor 1, activate platelets to give Ca(++) signals, aggregation, and release of granule contents. Platelet aggregation was dependent on release of adenosine diphosphate (ADP) and its interaction with platelet ADP receptors. Part, but not all, of the Ca(++) signal was due to ADP release feeding back to its receptors. Platelet activation also involved heparan or chondroitin sulfate associated with the platelet surface and was inhibited by cleavage of these glycosaminoglycans or by heparin or low molecular weight heparin. These platelet receptors may be involved in inflammatory or allergic responses or in platelet activation in human immunodeficiency virus infection.
已知血小板含有血小板因子4和β-血小板球蛋白，这两种α-趋化因子含有CXC基序，但最近的研究将范围扩展到了以CC基序为特征的β家族趋化因子，包括RANTES和Gro-α。也有证据表明血小板中存在趋化因子受体CCR4和CXCR4。本研究表明血小板具有功能性CCR1、CCR3、CCR4和CXCR4趋化因子受体。聚合酶链反应在血小板RNA中检测到趋化因子受体信使RNA。CCR1、CCR3，尤其是CCR4给出了强信号；CXCR1和CXCR4呈弱阳性。用特异性抗体进行的流式细胞术显示CXCR4存在清晰信号，CCR1和CCR3存在微弱信号，而CXCR1、CXCR2、CXCR3和CCR5均为阴性。用针对细胞质肽的多克隆抗体进行免疫沉淀和蛋白质印迹分析清楚地表明，血小板中存在CCR1和CCR4，其含量分别与单核细胞和CCR4转染细胞相当。针对这些受体的特异性趋化因子，包括单核细胞趋化蛋白1、巨噬细胞炎性肽1α、嗜酸性粒细胞趋化因子、RANTES、TARC、巨噬细胞衍生趋化因子和基质细胞衍生因子1，可激活血小板产生Ca(++)信号、聚集并释放颗粒内容物。血小板聚集依赖于二磷酸腺苷（ADP）的释放及其与血小板ADP受体的相互作用。部分（但不是全部）Ca(++)信号是由于ADP释放反馈至其受体所致。血小板激活还涉及与血小板表面相关的硫酸乙酰肝素或硫酸软骨素，并且可被这些糖胺聚糖的裂解或肝素或低分子量肝素所抑制。这些血小板受体可能参与炎症或过敏反应，或参与人类免疫缺陷病毒感染中的血小板激活。
