Cartilage specific collagen activates macrophages and the alternative pathway of complement: Evidence for an immunopathogenic concept of rheumatoid arthritis

We studied the effect of human interstitial collagen types I, II, and III on serum-free cultured mouse macrophages and on the complement classical and alternative pathways in human and guinea-pig serum. Type II collagen produced a dose-dependent consumption and conversion of C3 and factor B both in the homologous and in the heterologous system. This effect on the alternative pathway was reproduced in genetically C4-deficient guinea-pig serum and could be triggered by native, triple helical type II molecules, by their component α chains, and the CNBr peptide mixture. Addition of type II collagen to the mouse macrophage cultures induced not only a dose- and time-dependent secretion of lysosomal enzymes, but also the generation of a supernatant factor cytotoxic for mouse mastocytoma P 815 cells. Collagen of types I and III were conspicuously less active or inactive in all assays. The studies demonstrate properties of the collagen specific for cartilage which, on a molecular level, suggest its direct, local participation in the production and perpetuation of rheumatoid arthritis.