Identification of a third component of complement-binding glycoprotein of human platelets.

Utilizing affinity chromatography, a C3-specific binding protein was isolated from 125I surface-labeled human platelets. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated two bands with mean Mr of 64,000 and 53,000, characteristic variability in the relative density of the two bands in a given individual, and the presence of N-linked complex oligosaccharides as well as sialic acid residues not associated with N-linked sugars. These characteristics are similar to those of a human leukocyte iC3- and C3b-binding glycoprotein, termed gp45-70. Further analysis showed that leukocyte gp45-70 and the platelet C3-binding glycoprotein have identical Mr and other similar structural features. Functional characterization of solubilized platelet preparations indicated that gp45-70 has cofactor activity. This membrane glycoprotein is structurally and antigenically distinct from decay accelerating factor (DAF), a complement regulatory protein previously identified on human platelet membranes. DAF and gp45-70 have complementary activity profiles inasmuch as DAF can prevent assembly of and dissociate the C3 convertases but has no cofactor activity, whereas gp45-70 has cofactor activity but no decay accelerating activity. We suggest that these two proteins function conjointly to prevent autologous complement activation.