Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets
Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets
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DOI：
10.1182/blood.v96.1.50.013k40_50_57
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发表时间：
2000-07-01
期刊：
影响因子：
20.3
通讯作者：
Poncz, M
中科院分区：
文献类型：
--
作者：
Kowalska, MA;Ratajczak, MZ;Poncz, M
血小板在血栓形成和炎症中发挥作用，在炎症部位释放的趋化因子可能激活血小板。在血小板上表达的趋化因子受体中，CXCR 4是趋化因子基质细胞衍生因子-1（SDF-1）的受体，CCR 4是巨噬细胞衍生趋化因子（MDC）的受体。在测试的趋化因子中，SDF-1和MDC是仅有的两种激活血小板的趋化因子。两者都是弱激动剂，但它们增强了对低剂量腺苷5'-二磷酸（ADP）、肾上腺素或5-羟色胺的反应。当SDF-1和MDC一起加入时，发生充分和活跃的血小板聚集。这两种趋化因子的血小板活化似乎涉及不同的途径：SDF-1抑制前列腺素（PG）I-2后环磷酸腺苷（cAMP）的增加，而MDC无影响。相比之下，MDC而不是SDF-1导致血小板的Ca ++动员。此外，富含血小板的血浆中MDC诱导的第二波聚集被阿司匹林、ADP清除剂磷酸肌酸/创造性磷酸激酶（CP/CPK）和ARL-66096（一种参与腺苷酸环化酶抑制的ADP P2T（AC）受体拮抗剂）抑制。而ADP P2Y受体抑制剂A3P5PS对聚集无影响。SDF-1诱导的聚集被阿司匹林抑制，但CP/CPK、ARL-66096或A3P5PS仅轻微影响。最后，测定血小板中趋化因子的存在。逆转录聚合酶链反应研究与血小板RNA没有检测到SDF-1或MDC的存在。总之，SDF-1和MDC是激活不同细胞内途径的血小板激动剂。它们在炎症部位血栓形成中的重要性需要进一步评估。（血。2000; 96：50 - 57）（C）2000年由美国血液学会。
Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5'-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I-2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++ mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2T(AC) receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1-induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase-polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated. (Blood. 2000;96:50-57) (C) 2000 by The American Society of Hematology.