Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets
Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets
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DOI：
10.1161/01.cir.95.10.2387
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发表时间：
1997-05-20
期刊：
影响因子：
37.8
通讯作者：
Schomig, A
中科院分区：
文献类型：
--
作者：
Neumann, FJ;Marx, N;Schomig, A
背景 活化的血小板束缚并活化髓系白细胞。为了研究这一机制在急性心肌梗死 (AMI) 中的潜在相关性，我们检查了 AMI 患者中白细胞-血小板粘附诱导的细胞因子以及白细胞-血小板缀合物的发生情况。方法和结果 我们在直接经皮腔内冠状动脉成形术 (PTCA) 之前和术后 5 天内每天采集 20 名 AMI 患者的外周静脉血样本，以及 20 名接受选择性 PTCA 的患者的外周静脉血样本。在整个研究期间，白细胞 CD41 免疫荧光（流式细胞术）显示，与对照患者相比，AMI 患者的白细胞-血小板粘附力增加（PTCA 前荧光[通道]的平均值 +/- SE：77 +/- 16 与 35 +/- 9；P = .003）。在体外，凝血酶刺激的固定血小板与中性粒细胞和单核细胞结合。 2 小时内，这导致普通白细胞中白细胞介素 (IL)-1 β、IL-8 的 mRNA 增加，单核细胞浓度含量增加，趋化蛋白 (MCP)-1 含量增加。 4小时后，无细胞上清液中IL-1β和IL-8浓度分别增加了268+/-36%和210+/-7%，细胞MCP-1含量增加了170+/-8%。将活化的血小板添加到贴壁单核细胞中也有类似的效果，并且与核因子-κ B 活化相关。抗P-选择素抗体对结合的抑制降低了活化血小板对细胞因子产生的影响。结论在AMI患者中，白细胞-血小板粘附增加。活化血小板的结合会诱导白细胞中的 IL-1β、IL-8 和 MCP-1。我们的研究结果表明，白细胞-血小板粘附有助于调节 AMI 中的炎症反应。
Background Activated platelets tether and activate myeloid leukocytes. To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI.Methods and Results We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 Versus 35 +/- 9; P = .003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL)-1 beta, IL-8, and monocyte concentration content increased chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively, and cellular MCP-1 content had increased by 170 +/- 8%. Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation. Inhibition of binding by anti-P-selectin antibodies reduced the effect of activated platelets on cytokine production.Conclusions In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.