OBJECTIVES Platelets are important regulators of vascular thrombosis and inflammation and are known to express Toll-like receptors (TLRs). Through TLRs, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate in vitro peripheral blood mononuclear cells (PBMCs) and granulocyte responses to TLR4, TLR2/1 and TLR2/6 stimulation in healthy subjects. METHODS Peripheral blood mononuclear cells and granulocytes from 10 healthy volunteers were cultured alone or cocultured with platelets. Cultures were left unstimulated or stimulated with 1 or 100 ng mL-1 of either LPS (TLR4 agonist), Pam3CSK4 (TLR2/1 agonist) or fibroblast-stimulating lipopeptide (FSL)-1 (TLR2/6 agonist). Neutrophil activation (CD66b expression), monocyte activation (HLA-DR), granulocyte elastase production and PBMC cytokine and chemokine production were examined. RESULTS Platelet coculture decreased neutrophil CD66b expression in response to LPS, Pam3CSK4 and FSL-1, and modestly decreased monocyte HLA-DR expression in response to low-dose LPS. Platelets reduced granulocyte elastase secretion in response to low doses of all TLR agonists tested. In response to LPS, platelet coculture reduced IL-6, tumor necrosis factor (TNF)-α and MIP-1β production, and increased IL-10 production by PBMCs. In response to FSL-1, platelets increased IL-6, IL-10 and MIP-1β production, but reduced TNF-α production. Platelet coculture did not alter PBMC cytokine/chemokine production in response to Pam3CSK4. CONCLUSION This study challenges the notion that platelets act solely in a pro-inflammatory manner. Rather, platelets are complex immunomodulators that regulate leucocyte responses to TLR stimulation in a TLR agonist-specific manner. Platelets may modulate leucocyte responses to dampen inflammation, and this platelet effect may play an important role in reducing inflammation-mediated host damage.

中文翻译：

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血小板调节白细胞对 Toll 样受体刺激的反应。

目的 血小板是血管血栓形成和炎症的重要调节因子，已知可表达 Toll 样受体 (TLR)。通过 TLR，血小板通过与白细胞相互作用介导许多反应。在这里，我们报告了血小板对健康受试者体外外周血单个核细胞 (PBMC) 和粒细胞对 TLR4、TLR2/1 和 TLR2/6 刺激反应的调节程度。方法将10名健康志愿者的外周血单个核细胞和粒细胞单独培养或与血小板共培养。不刺激培养物或用 1 或 100 ng mL-1 LPS（TLR4 激动剂）、Pam3CSK4（TLR2/1 激动剂）或成纤维细胞刺激性脂肽 (FSL)-1（TLR2/6 激动剂）刺激培养物。中性粒细胞活化（CD66b 表达），单核细胞活化（HLA-DR），检查粒细胞弹性蛋白酶的产生和PBMC细胞因子和趋化因子的产生。结果 血小板共培养降低了响应 LPS、Pam3CSK4 和 FSL-1 的中性粒细胞 CD66b 表达，并适度降低了响应低剂量 LPS 的单核细胞 HLA-DR 表达。血小板响应于所有测试的低剂量 TLR 激动剂而减少粒细胞弹性蛋白酶的分泌。作为对 LPS 的反应，血小板共培养减少了 IL-6、肿瘤坏死因子 (TNF)-α 和 MIP-1β 的产生，并增加了 PBMCs 的 IL-10 的产生。作为对 FSL-1 的反应，血小板增加了 IL-6、IL-10 和 MIP-1β 的产生，但减少了 TNF-α 的产生。血小板共培养没有改变响应 Pam3CSK4 的 PBMC 细胞因子/趋化因子的产生。结论 本研究挑战了血小板仅以促炎方式起作用的观点。相当，血小板是复杂的免疫调节剂，以 TLR 激动剂特异性方式调节白细胞对 TLR 刺激的反应。血小板可以调节白细胞对抑制炎症的反应，这种血小板作用可能在减少炎症介导的宿主损伤方面发挥重要作用。