title: Platelet activation induces increased Fc gamma receptor expression.
abstract: 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.
authors: Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors: K R
authors: KR
authors: McCrae
authors: S J
authors: SJ
authors: Shattil
authors: D B
authors: DB
authors: Cines
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D015539:Platelet Activation; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D000244:Adenosine Diphosphate; D013806:Theophylline; D011464:Epoprostenol; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine