EXPRESSION AND ROLE OF CYCLOOXYGENASE ISOFORMS IN ALVEOLAR AND PERITONEAL-MACROPHAGES

Prostaglandin synthesis represents one means by which macrophages modu late inflammation. The initial enzyme in the metabolism of arachidonic acid to prostaglandins is cyclooxygenase (COX). Both constitutive (CO X-1) and inducible (COX-2) isoforms are recognized. We previously show ed that COX activity of rat peritoneal macrophages (PM) exceeds that o f alveolar macrophages (AM). In this study, we correlated the steady-s tate levels of COX-1 and COX-2 proteins with COX activity in resident AM and PM. Freshly obtained AM contained lower levels of COX-1 than di d fresh PM. Neither contained substantial amounts of COX-2 in the basa l state, but both cell types demonstrated induction when cultured with lipopolysaccharide; once again, COX-2 levels in PM exceeded those in AM. Despite COX-2 induction under these circumstances, its contributio n to prostaglandin production appeared to be modest. We conclude that, although both isoforms of COX are expressed in rat AM and PM, COX-1 i s responsible for the majority of enzyme activity in both the basal an d stimulated states. The lesser prostaglandin synthetic capacity of AM than of PM appears to be the consequence of lower steady-state levels of both COX proteins.