C3d fragment of complement interacts with laminin and binds to basement membranes of glomerulus and trophoblast.
Two mouse monoclonal antibodies generated against human placental homogenate were found to react specifically with human complement component C3. In immunofluorescence of human tissues, these antibodies gave a bright linear staining outlining the glomerular basement membrane of the adult kidney and the trophoblast basement membrane of placenta. An identical staining pattern was observed with a rabbit C3d antiserum which also prevented binding of the monoclonal antibodies to tissue sections. Only negligible basement membrane staining was observed in the same tissues with antisera to human C3c, C5, IgG, IgA, or IgM. When interactions of C3 with basement membrane proteins were tested in enzyme immunoassays and column chromatography, C3(H2O) was found to bind efficiently to solid-phase laminin. Native C3 from fresh plasma did not bind to laminin but C3 from plasma treated with methylamine bound efficiently. When C3 was cleaved with trypsin, C3b and C3d but not C3c bound to laminin-Sepharose. The interaction of C3 and laminin was inhibited by soluble laminin and by high ionic strength. The results indicate that C3d, a biologically active breakdown product of C3, can be found in glomerular and placental basement membranes in the absence of signs for ongoing local complement activation or immune complex deposition. It is possible that binding affinities between C3 and basement membrane molecules, especially laminin, are involved in the retention of C3d at these sites. Such interactions between C3 and components of the glomerular basement membrane could play important roles in complement-related pathological processes of the glomerulus.
D000911:Antibodies, Monoclonal / Q000276:immunology; D001485:Basement Membrane / Q000378:metabolism*; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism*; D015933:Complement C3d; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D014327:Trophoblasts / Q000378:metabolism* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D003176:Complement C3; D007797:Laminin; D015933:Complement C3d