We examined prostaglandin E2 (PGE2) biosynthetic heterogeneity in fibroblast substrains and possible mechanisms that might mediate this heterogeneity. PGEz synthesis of fibroblast substrains, in response to phytohemagglutinin-stimulated mononuclear cell supernates, ranged from 9.0 f 1.0 ng/ml to 79.3 2 7.4 ng/ml (mean f SD). The phenotypic behavior of individual substrains was stable. Substrains were also heterogeneous in PGE2 response to phorbol myristate acetate, and displayed stability in this phenotype as well. Substrains which were high responders to mononuclear cell supernate also ranked high in response to phorbol myristate acetate. Similar heterogeneity was observed in response to purified interleukin-1. Arachidonic acid added exogenously did not raise interleukin-1 responsiveness of low-producer substrains to that of high producers, suggesting that differences in PGE2 synthesis among substrains did not reflect differences in substrate availability or phospholipase activity. Supernates of high-and low-responder phenotype substrains, when added to cells of the reciprocal strain or to unrelated fibroblasts, did not affect the pattern of PGEz synthesis. The concordance of substrain responsiveness to mononuclear cell supernate and phorbol myristate acetate suggests that heterogeneity among substrains in PGE2
From the Division of Rheumatic Diseases, Veterans Ad-