COMPLEMENT COMPONENTS C1Q, C1R/C1S, AND C1INH IN RHEUMATOID-ARTHRITIS - CORRELATION OF IN-SITU HYBRIDIZATION AND NORTHERN BLOT RESULTS WITH FUNCTION AND PROTEIN CONCENTRATION IN SYNOVIUM AND PRIMARY CELL CULTURES

Objective, To analyze the synovial site and the cell types expressing Clq, C1q/C1s, and C1-esterase inhibitor (C1INH) and to characterize newly synthesized Clq in patients with rheumatoid arthritis (RA), Methods, Tissue and primary cell cultures of synovium from RA patients were analyzed for Clq, C1r/C1s, and C1INH by Northern blotting, in situ hybridization, and pulse-chase experiments for Clq, Results, The de novo synthesis of Clq, C1r/C1s, and C1INH in synovium and primary cell cultures was proven by Northern blot and by antigenic and functional analysis, In in situ hybridization experiments, the synovial lining cell layer was identified as the site of Clq, Clr, and C1INH expression, In contrast, immunohistologic analysis showed that Clq, Cls, and C1INH proteins were present in a thin film covering the synovial lining cells, In situ hybridization performed on primary cell cultures provided evidence that only macrophages were able to express Clq, whereas fibroblasts and stellate cells synthesized Clr, Conclusion, The synovium is important for the synthesis and secretion of Clq and C1r/C1s, as well as the control protein C1INH, which supports the idea of a locally occurring inflammatory process in RA patients.