Platelet activation induces increased Fc gamma receptor expression
Mccrae, K.R.; Shattil, S.J.; Cines, D.B.
Journal of Immunology 144(10): 3920-3927
1990
ISSN/ISBN: 0022-1767 PMID: 2139675 Document Number: 350852
Platelets 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 platlets from nine healthy donors expressed a mean of 891 Fc.gamma.R per platelet, whereas platelets activated at 25.degree.C by thrombin or PMA expressed a mean of 1382 Fc.gamma.R per cell, an average increase of 55% (p < 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.degree.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.