E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils
E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils
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DOI：
10.1182/blood-2005-09-3803
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Walker, Trevor R.
中科院分区：
文献类型：
--
作者：
McMeekin, Sarah R.;Dransfield, Ian;Walker, Trevor R.
选择素分子家族（L-、P-和E-选择素）介导白细胞和内皮细胞之间的粘附相互作用，这是将白细胞募集到炎症部位所需的。可溶性 E-选择素水平在炎症性疾病中升高，并通过延长 Ca2+ 动员来促进中性粒细胞 β(2)-整合素介导的粘附。虽然单独的可溶性 E-选择素无法启动 Ca2+ 信号传导，但在初始血小板活化因子 (PAF) 诱导的肌醇 1,4,5-三磷酸 ON 敏感储存中释放 Ca2+ 后，它允许一种新的“允许”储存操作钙进入 (SOCE)。这种对可溶性 E-选择素和 PAIF 的许可性 SOCE 的诱导被证明是通过与百日咳毒素不敏感的 G(q/11) 偶联的 G 蛋白偶联受体 (GPCR) 发挥作用。此外，我们证明了许可性 SOCE 由规范瞬时受体电位通道 (TRPC) 介导，因为它对 MRS1845 和 Gd3+ 的特异性抑制敏感，并且 TRPC6 是人类中性粒细胞表达的主要 TRPC 家族成员。在机制方面，我们证明了可溶性E-选择素激活了Src家族酪氨酸激酶，这是一种在中性粒细胞暴露于PAR后调节许可性SOCE的信号通路中磷脂酰肌醇T激酶的上游效应。 总之，本报告为炎症介质和粘附受体之间在分子水平上的沟通提供了第一个证据，通过选择素受体连接，允许在PAF刺激人中性粒细胞后发生许可性SOCE。
The selectin family of molecules (L-, P-, and E-selectin) mediates adhesive interactions between leukocytes and endothelial cells required for recruitment of leukocytes to inflammatory sites. Soluble E-selectin levels are elevated in inflammatory diseases and act to promote neutrophil beta(2)-integrin-mediated adhesion by prolonging Ca2+ mobilization. Although soluble E-selectin alone was unable to initiate Ca2+ signaling, it allowed a novel "permissive" store-operative calcium entry (SOCE) following the initial platelet-activating factor (PAF)-induced release of Ca2+ from inositol 1,4,5-trisphosphate ON-sensitive stores. This induction of permissive SOCE in response to soluble E-selectin and PAIF was shown to act through a G protein-coupled receptor (GPCR) coupled to pertussis toxin-insensitive G(q/11). Furthermore, we demonstrated that permissive SOCE was mediated by canonical transient receptor potential channel (TRPC) due to its sensitivity to specific inhibition by MRS1845 and Gd3+ and that TRPC6 was the principal TRPC family member expressed by human neutrophils. In terms of mechanism, we demonstrated that soluble E-selectin activated Src family tyrosine kinases, an effect that was upstream of phosphatidylinositol T-kinase in a signaling pathway that regulates permissive SOCE following exposure of neutrophils to PAR In summary, this report provides the first evidence for communication between an inflammatory mediator and adhesion receptors at a molecular level, through selectin receptor ligation allowing permissive SOCE to occur following PAF stimulation of human neutrophils.