McCrae K R, Shattil S J, Cines D B
Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
J Immunol. 1990 May 15;144(10):3920-7.
Platelet contain Fc gamma RII. However, little is known about how the expression of these receptors is regulated. Inasmuch as platelet activation by a variety of agonists increases the expression of several proteins on the platelet surface, we used flow cytometry to study the effect of platelet activation on the expression of platelet Fc gamma R by measuring the binding of fluorescein-labeled oligomeric IgG (FITC-IgG oligomer) and fluorescein-labeled mAb IV.3 (FITC-IV.3), a mAb that recognizes Fc gamma RII, to platelets. The number of Fc gamma R per platelet was determined by relating the binding to platelets of FITC-IV.3, measured by flow cytometry, to the binding of 125I-labeled IV.3, measured using a standard filtration assay. Nonactivated, gel-filtered platelets from nine healthy donors expressed a mean of 891 Fc gamma R per platelet, whereas platelets activated at 25 degrees C by thrombin or PMA expressed a mean of 1382 Fc gamma R an average increase of 55% (p less than 0.001). Binding of FITC-IgG oligomer increased to a similar extent when platelets were stimulated by these agonists. A smaller increase in the number of Fc gamma R expressed on the platelet surface was measured when platelets were stimulated with ADP, though no increase was observed with epinephrine. The agonist-dependent increase in Fc gamma R expression did not occur when platelets were studied at 4 degrees C or in the presence of agents that elevate intracellular levels of cAMP, suggesting that platelet activation was required for this process. Agonist-stimulated Fc gamma R expression did not depend on dense-granule secretion, because it was observed at low agonist concentrations in the absence of 14C-serotonin release. These studies demonstrate that the number of Fc gamma R expressed on the platelet surface increases when platelets are activated by several agonists, perhaps as a result of the exposure of Fc gamma R located along the surface-connected open canalicular system, or the fusion of platelet alpha-granule and plasma membranes during the activation process. Increased Fc gamma R expression may promote the clearance of IgG-containing immune complexes from the circulation, and contribute to the development of immune complex-mediated thrombocytopenia.
血小板含有FcγRII。然而，关于这些受体的表达是如何调控的却知之甚少。由于多种激动剂激活血小板会增加血小板表面多种蛋白质的表达，我们使用流式细胞术，通过测量荧光素标记的寡聚IgG（FITC-IgG寡聚物）和荧光素标记的单克隆抗体IV.3（FITC-IV.3，一种识别FcγRII的单克隆抗体）与血小板的结合，来研究血小板激活对血小板FcγR表达的影响。通过将流式细胞术测量的FITC-IV.3与血小板的结合量与使用标准过滤测定法测量的125I标记的IV.3的结合量相关联，来确定每个血小板上FcγR的数量。来自9名健康供体的未激活、经凝胶过滤的血小板平均每个血小板表达891个FcγR，而在25℃下被凝血酶或佛波酯激活的血小板平均表达1382个FcγR，平均增加55%（p<0.001）。当血小板被这些激动剂刺激时，FITC-IgG寡聚物的结合也有类似程度的增加。当用ADP刺激血小板时，血小板表面表达的FcγR数量有较小增加，而用肾上腺素刺激时未观察到增加。当在4℃下研究血小板或在存在提高细胞内cAMP水平的试剂时，未出现激动剂依赖性的FcγR表达增加，这表明该过程需要血小板激活。激动剂刺激的FcγR表达不依赖于致密颗粒分泌，因为在低激动剂浓度下且无14C-5-羟色胺释放时也观察到了这种现象。这些研究表明，当血小板被多种激动剂激活时，血小板表面表达的FcγR数量会增加，这可能是由于位于表面连接的开放小管系统中的FcγR暴露，或者是激活过程中血小板α颗粒与质膜融合的结果。FcγR表达的增加可能促进含IgG免疫复合物从循环中的清除，并有助于免疫复合物介导的血小板减少症的发生。
