Human platelet-immune complex interaction in plasma.
The plasmas of four patients with SLE were found to contain two anti-DNA antibody populations of widely varying affinity. The addition of double-stranded DNA to the anti-DNA plasmas resulted in formation of precipitating (insoluble) and soluble immune complexes. Human platelets suspended at physiologic concentrations in the anti-DNA plasmas during the immune complex formation underwent aggregation and release that correlated positively with precipitating (insoluble) immune complex formation but not with soluble complex formation. Preformed insoluble immune complexes induced platelet aggregation and release in a significant linear fashion, and release was inhibited by increasing concentrations of soluble immune complexes or Fc-fragments. The release reaction was completely inhibited by blocking the Fc-pieces of the preformed insoluble DNA-anti-DNA immune complexes. Soluble complexes of DNA-anti-DNA and A-anti-A at equimolar IgG concentrations produced similar degrees of inhibition, which were much greater than equimolar concentrations of Fc-fragments. The ability of increasing concentrations of soluble immune complex formed at fixed antibody concentration to cause greater inhibition of platelet release suggests that occupancy of the antigen binding sites of the antibody increases its ability to block the platelet Fc-receptor. The inhibition is similar for soluble complexes of varying antigen molecular size. This is compatible with the concept that a conformational change in the antibody occurs after antigen binding and results in an increase in binding strength at the platelet Fc-receptor site. We conclude that insoluble DNA-anti-DNA immune complexes induce aggregation and release of human platelets at physiologic concentrations in plasma via the platelet Fc-receptor.
D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D003165:Complement System Proteins / Q000032:analysis; D004247:DNA / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010974:Platelet Aggregation; D011961:Receptors, Fc / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D003165:Complement System Proteins; D004247:DNA