Haimovich B, Regan C, DiFazio L, Ginalis E, Ji P, Purohit U, Rowley R B, Bolen J, Greco R
Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
J Biol Chem. 1996 Jul 5;271(27):16332-7. doi: 10.1074/jbc.271.27.16332.
Platelets express a single low affinity receptor for immunoglobulin, FcgammaRII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to IgG was blocked by the FcgammaRII receptor-specific monoclonal antibody, IV. 3. Pretreatment of the platelets with cytochalasin D to inhibit actin polymerization similarly prevented cell binding to IgG having no effect on platelet binding to fibrinogen. Platelet adhesion to IgG also led to the induction of tyrosine phosphorylation of multiple proteins including pp125(FAK) and p72(SYK). These proteins were also tyrosine-phosphorylated in alphaIIbbeta3-deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that FcgammaRII mediates pp125(FAK) phosphorylation and platelet adhesion to IgG independent of the integrin alphaIIbbeta3. Treatment of the platelets with bisindolylmaleimide to inhibit protein kinase C prevented phosphorylation of pp125(FAK) as well as several other proteins, but not p72(SYK) phosphorylation. This study establishes that the FcgammaRII receptor mediates pp125(FAK) phosphorylation via protein kinase C.
血小板表达一种单一的低亲和力免疫球蛋白受体FcγRII，该受体在与多价免疫复合物相互作用时会触发多种细胞反应。在本研究中，我们发现固定化的IgG也是血小板活化的有效刺激物，可触发黏附、聚集、大量致密颗粒分泌和血栓素生成。血小板与IgG的黏附被FcγRII受体特异性单克隆抗体IV.3阻断。用细胞松弛素D预处理血小板以抑制肌动蛋白聚合，同样可阻止细胞与IgG结合，而对血小板与纤维蛋白原的结合没有影响。血小板与IgG的黏附还导致多种蛋白质的酪氨酸磷酸化，包括pp125（黏着斑激酶）和p72（脾酪氨酸激酶）。在患有Glanzmann血小板无力症患者的αIIbβ3缺陷型IgG黏附血小板中，这些蛋白质也发生了酪氨酸磷酸化。这些数据表明，FcγRII介导pp125（黏着斑激酶）磷酸化以及血小板与IgG的黏附，且不依赖于整合素αIIbβ3。用双吲哚马来酰胺处理血小板以抑制蛋白激酶C，可阻止pp125（黏着斑激酶）以及其他几种蛋白质的磷酸化，但不影响p72（脾酪氨酸激酶）的磷酸化。本研究证实，FcγRII受体通过蛋白激酶C介导pp125（黏着斑激酶）磷酸化。
