Connective tissue activation

Connective tissue a ctivating p eptides from lymphocytes (CTAP-I) and platelets (CTAP-III) are known to stimulate glycosaminoglycan synthesis, glycolysis, and mitogenesis in connective tissue cell cultures. Direct evidence suggested that increased accumulation of cyclic AMP was involved in the action of these peptide agonists, and increased prostaglandin E synthesis was postulated on the basis of indirect evidence. In the present experiments, CTAP-I and -III were incubated with human and murine cells in culture, and prostaglandin E was measured by radioimmunoassay using antibody directed primarily to prostaglandin E2. Both CTAP-I and -III markedly stimulated the elaboration of prostaglandin E into culture medium, the earliest evidence of increased synthesis occurring at 4 hours with maximal concentrations found at 24 hours. Substantial residual stimulation persisted at least through 48 hours. Indo-methacin (13.0 Mg/ml) obliterated basal and incremental synthesis of prostaglandin in the presence of mediators. Cycloheximide (8.7 Mg/ml) did not affect the stimulation of prostaglandin synthesis by CTAP-I and -III. Three nonrheumatoid and 3 rheumatoid synovial cell strains showed similar basal levels of prostaglandin E and similar responses to CTAP-I. A murine fibroblast cell strain (3T3) showed increased prostaglandin E synthesis on exposure to CTAP-I, and the KB tumor cell strain was markedly stimulated by CTAP-III. These studies confirm the increased synthesis of E series prostaglandins postulated to occur in human connective tissue cells on exposure to CTAP-I and -III, and clarify the mechanism of action of these agonists on “activated” target cells. The importance of elevated extracellular concentrations of prostaglandins is uncertain, although they may act directly on sensitive cell types as well as potentiate the actions of CTAP-I and -III on neighboring cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37752/1/1780240309_ftp.pd