LOCALIZATION OF APOPTOSIS AND EXPRESSION OF APOPTOSIS RELATED PROTEINS IN THE SYNOVIUM OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objectives-To investigate whether apoptosis occurs in the synovium of rheumatoid arthritis (RA), and the intermediate molecules operating in this process. Methods-DNA fragmentation was detected by in situ nick end labelling (ISNEL) in the synovium of patients with RA (n = 11) and control patients with femoral neck fracture (n = 5). The expression o f proteins p53, p21(WAF1/CIP1), c-myc, proliferating cell nuclear anti gen (PCNA), and Bcl-2 was also examined by immunohistochemistry. Resul ts-ISNEL positive synovial cells with apoptosis specific morphology we re detected in extremely limited areas in only two RA synovial tissue specimens. Proteins p53, p21(WAF1/CIP1), and c-myc, known inducers of apoptosis or cell cycle arrest or both, were expressed in the sublinin g cells independent of ISNEL positive cells. PCNA, a marker for cell p roliferation, was observed in the synovial lining cells. Bcl-2, an inh ibitor of apoptosis, was expressed mainly in infiltrated lymphocytes a nd in parts of the sublining layer cells of RA; it also did not corres pond with ISNEL staining. Conclusions-Our findings indicate that RA sy novial cells undergo apoptosis in addition to cell. proliferation, but the frequency of apoptosis was very low. We suspect that the apoptoti c process in the RA synovium may be suppressed by overexpression of Bc l-2. Although expressed proteins p53, p21(WAF1/CIP1), and c-myc were p resent in the RA synovium, these protooncogenes are probably not impli cated in the apoptotic process.