DEGRADATION OF COMPLEMENT COMPONENT C3 IN JOINT FLUIDS FROM RHEUMATOID-ARTHRITIS PATIENTS IS INDUCED BY CATHEPSIN-G AND CONSECUTIVE FACTOR-H AND FACTOR-I OF THE COMPLEMENT-SYSTEM

The cleavage of the complement component C3 in synovial fluids (SF) fr om patients with rheumatoid arthritis (RA) was studied in vitro, using the I-125-labeled purified protein. I-125-C3, when incubated in paire d samples of SF and plasma from RA patients, showed a more pronounced degradation in SF than in plasma, but leading to the C3 fragmentation observed during normal complement activation. The regulatory protein f actor H (FH) was also radiolabeled and incubated in the same samples. In this case, no degradation of the protein was observed. To test the functional activity of FH in these biological fluids, I-125-C3b and an antihuman FH polyclonal antibody were used in a cofactor assay. As a result, FH was fully able to function as cofactor in the inactivation of C3b into iC3b. Finally, three major proteolytic enzymes present in the joint fluids (collagenase, elastase and cathepsin G) were tested f or their effect on native C3 and on FH in control experiments without biological fluids. We observed that elastase and cathepsin G, but not collagenase, cleaved initially C3 into a C3b-like fragment and then to smaller split fragments. Only elastase had a proteolytic activity on FH. It is concluded that, in SF of RA patients, a C3b-like fragment is generated by a protease. This C3b can be processed by the functionall y active FH and FI present in SF. Since FH remains unaltered in SF, th e action of elastase is unlikely and cathepsin G is a good candidate f or the C3 cleavage observed.