Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human platelets
Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human platelets
复制标题
DOI：
10.1111/j.1365-2141.2008.06999.x
复制
发表时间：
2008-04-01
影响因子：
6.5
通讯作者：
Garraud, Olivier
中科院分区：
文献类型：
--
作者：
Cognasse, Fabrice;Hamzeh-Cognasse, Hind;Garraud, Olivier
血小板连接止血和炎症的过程。本研究检测了血小板表面Toll样受体4（TLR 4）结合后释放的免疫调节因子。在存在或不存在针对人TLR 4的阻断性单克隆抗体的情况下，将单克隆抗人Fc γ RII Ab（IV.3）处理的人血小板与TLR 4配体一起培养。sCD 62 p、表皮生长因子（EGF）、转化生长因子β（TGF β）、白细胞介素（IL）-8、血小板活化因子4（PAF 4）、血小板衍生生长因子、α、β多肽（PDGF-AB）、血管生成素、RANTES（活化后调节，正常T细胞表达，推测分泌）和sCD 40 L的释放通过特异性酶联免疫吸附试验进行测量。TLR 4配体[大肠杆菌脂多糖（LPS）]结合血小板TLR 4，其差异调节血小板释放细胞因子。值得注意的是，（i）sCD 62 p、IL-8、EGF和TGF β释放各自独立于TLR 4接合后的血小板活化;（ii）RANTES、血管生成素和PDGF-AB浓度在TLR 4接合后的血小板上清液中较弱;（iii）sCD 40 L和PAF 4在由TLR 4配体刺激的血小板释放中以大浓度存在。E.通过用抗TLR 4单克隆抗体预孵育血小板来减弱大肠杆菌对分泌因子的调节，这与TLR 4受体特异性介导的免疫调节一致。我们认为，血小板适应随后的反应，极化细胞因子分泌后，TLR 4参与。
Blood platelets link the processes of haemostasis and inflammation. This study examined the immunomodulatory factors released by platelets after Toll-Like Receptor 4 (TLR4) engagement on their surfaces. Monoclonal anti-human Fc gamma RII Ab (IV.3)-treated human platelets were cultured with TLR4 ligands in the presence or absence of blocking monoclonal antibody to human TLR4. The release of sCD62p, epidermal growth factor (EGF), transforming growth factor beta (TGF beta), interleukin (IL)-8, platelet activating factor 4 (PAF4), platelet-derived growth factor, alpha, beta polypeptide (PDGF-AB), Angiogenin, RANTES (regulated upon activation, normal T-cell expressed, and presumably secreted) and sCD40L were measured by specific enzyme-linked immunosorbent assay. TLR4 ligand [Escherichia coli lipopolysaccharide (LPS)] bound platelet TLR4, which differentially modulates the release of cytokines by platelets. It was noted that (i) sCD62p, IL-8, EGF and TGF beta release were each independent of platelet activation after TLR4 engagement; (ii) RANTES, Angiogenin and PDGF-AB concentration were weaker in platelet supernatant after TLR4 engagement; (iii) sCD40L and PAF4 are present in large concentration in the releaseate of platelets stimulated by TLR4 ligand. The effects of LPS from E. coli on the modulation of secretory factors were attenuated by preincubation of platelets with an anti-TLR4 monoclonal antibody, consistent with the immunomodulation being specifically mediated by the TLR4 receptor. We propose that platelets adapt the subsequent responses, with polarized cytokine secretion, after TLR4 involvement.