Danese Silvio, de la Motte Carol, Reyes Brenda M Rivera, Sans Miquel, Levine Alan D, Fiocchi Claudio
Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
J Immunol. 2004 Feb 15;172(4):2011-5. doi: 10.4049/jimmunol.172.4.2011.
Platelets, in addition to exerting hemostatic activity, contribute to immunity and inflammation. The recent report that platelets express CD40 led us to hypothesize that CD40 ligand (CD40L)-positive T cells could bind to platelets, cause their activation, and trigger granular RANTES release, creating a T cell recruitment feedback loop. Platelets were cocultured with resting or activated autologous T cells and their activation was assessed by P-selectin expression. RANTES binding to endothelial cells was assessed by confocal microscopy, and its biological activity was demonstrated by a T cell adhesion assay. CD40L-positive T cells induced platelet activation through a contact-mediated, CD40-dependent pathway resulting in RANTES release, which bound to endothelial cells and mediated T cell recruitment. Soluble CD40L induced the same events via p38, but not extracellular signal-regulated kinase, phosphorylation. These results show the existence of a novel platelet-dependent pathway of immune response amplification which brings these nonimmune cells close to the level of pathogenic relevance traditionally attributed to classical immune cells.
血小板除了发挥止血活性外，还参与免疫和炎症反应。最近有报道称血小板表达CD40，这使我们推测CD40配体（CD40L）阳性T细胞可能与血小板结合，导致其活化，并触发颗粒性RANTES释放，从而形成T细胞募集反馈回路。将血小板与静息或活化的自体T细胞共培养，并通过P-选择素表达评估其活化情况。通过共聚焦显微镜评估RANTES与内皮细胞的结合，并通过T细胞黏附试验证明其生物学活性。CD40L阳性T细胞通过接触介导的、CD40依赖的途径诱导血小板活化，导致RANTES释放，RANTES与内皮细胞结合并介导T细胞募集。可溶性CD40L通过p38磷酸化而非细胞外信号调节激酶磷酸化诱导相同的事件。这些结果表明存在一种新的依赖血小板的免疫反应放大途径，使这些非免疫细胞接近传统上归因于经典免疫细胞的致病相关性水平。
