Immune Injury to Human Platelets Mediated By IgG Fc Receptor is Prevented by Prostacyclin

Immune injury to human platelets by drugs, bacteria, and viruses which form antigenantibody complexes is mediated by the IgG Fc receptor on human platelets and results in thrombocytopenia. We studied whether immune injury to human platelets mediated by the IgG Fc receptor can be prevented by prostacyclin (Prostagland in 1₂, PGI₂), a novel prost glandin generated by the blood vessel wall. Immune injury to human platelets in whole plasma was elicited by Protein A-bearing staphylococci. Protein A induces binding of I to the human platelet Fc receptor, which results in platelet aggregation and ³H-seroton release in whole plasma. Excess of isolated Fc fragment inhibits aggregation and serotonin release in this model of immune injury. Synthetic PGI₂ protected human platelets from this IgG Fc fragment-mediated immune injury in whole plasma. Inhibition was prompt (1 to 5 min) and dose dependent, reaching maximum at 10^-6M of PGI₂. Removal of plasma proteins and use of IgG-coated cells did not change the inhibitory potency of PGI₂, which was at least 1000-fold more active than 6-keto PGF_1α. Electron microscopy revealed than PGI₂ prevented binding of IgG- coated cel is to human platelet membrane. From comparison with anti-inflammatory steroids (methylprednisolone) and nonsteroidal prostaglandin synthetase inhibitors (ASA), it appears that prostacyclin is the most active agent known the date to protect human platelets from IgG Fc receptor-mediated immune injury in vitro.