Griffith L, Slupsky J, Seehafer J, Boshkov L, Shaw A R
Department of Medicine, University of Alberta, Edmonton, Canada.
Blood. 1991 Oct 1;78(7):1753-9.
Anti-CD9 monoclonal antibodies (MoAbs) are reported to activate human platelets through stimulation of the Fc gamma II receptor. We show here that nonstimulatory F(ab')2 fragments of the anti-CD9 MoAb 50H.19 induce dense-granule release and dose-dependent platelet aggregation when attached to polystyrene latex beads. Cross-linking F(ab')2 fragments of MoAb 50H.19 by F(ab')2 fragments of goat anti-mouse IgG does not result in platelet aggregation unless the second antibody is bound to latex beads, indicating that immobilization, and not cross-linking of the stimulus, is critical to the initiation of the CD9 signal. In contrast, F(ab')2 fragments of the second antibody readily induce the aggregation of platelets treated with the anti-Fc gamma II receptor MoAb IV.3. Immobilization of MoAb per se is insufficient to induce an activation signal because intact and F(ab')2 fragments of nonstimulatory MoAb directed to glycoprotein Ib and HLA class I do not become stimulatory when attached to beads. CD9-induced activation requires cytoskeletal rearrangement because it is inhibited by cytochalasin B. Aggregation is blocked by inhibitors of the thromboxane pathway, indicating that CD9 activates phospholipase C indirectly through prior activation of phospholipase A2.
据报道，抗CD9单克隆抗体（MoAbs）通过刺激FcγII受体来激活人血小板。我们在此表明，抗CD9 MoAb 50H.19的非刺激性F(ab')2片段附着于聚苯乙烯乳胶珠时，会诱导致密颗粒释放和剂量依赖性血小板聚集。用山羊抗小鼠IgG的F(ab')2片段交联MoAb 50H.19的F(ab')2片段不会导致血小板聚集，除非第二抗体与乳胶珠结合，这表明刺激物的固定而非交联对于启动CD9信号至关重要。相比之下，第二抗体的F(ab')2片段很容易诱导用抗FcγII受体MoAb IV.3处理过的血小板聚集。MoAb本身的固定不足以诱导激活信号，因为针对糖蛋白Ib和HLA I类的非刺激性MoAb的完整片段和F(ab')2片段附着于珠子时不会变得具有刺激性。CD9诱导的激活需要细胞骨架重排，因为它受到细胞松弛素B的抑制。聚集被血栓素途径的抑制剂阻断，这表明CD9通过磷脂酶A2的预先激活间接激活磷脂酶C。
