INFLAMMATORY AGONISTS INDUCE CYCLOOXYGENASE TYPE-2 EXPRESSION BY HUMAN NEUTROPHILS

The synthesis of prostanoids is regulated by cyclooxygenases (prostagl andin H synthases), which catalyze the conversion of arachidonic acid to PGH(2), Cyclooxygenases are the target of aspirin and other nonster oidal anti-inflammatory agents, In this study, we found that human pol ymorphonuclear leukocytes (PMNs) express the inducible isoform of cycl ooxygenase, COX-2, H hen stimulated by LPS whereas the protein nas not detectable in freshly isolated human PMNs. We also found by immunohis tochemical analysis that COX-2 is expressed in PMNs in inflamed human tissues, COX-2 was induced in a time-and concentration-dependent fashi on when isolated human PMNs were exposed to LPS; COX-2 was also induce d, or its expression was increased, by TNF-alpha, IL-1, and IL-8, Expr ession of COX-2 in stimulated PMNs was paralleled by secretion of PGE( 2). The release of PGE(2) was blocked by a selective nonsteroidal inhi bitor of COX-2, indicating that the enzyme is responsible for the pros tanoids produced, and was inhibited by dexamethasone. The time course of LPS-induced COX-2 expression and other features were different in f reshly isolated PMNs, monocytes, and macrophages, indicating that COX- 2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation, Consistent with this, IL-4 and IL -10, which suppressed LPS-induced COX-2 expression in monocytes, had l ittle effect on this response by PMNs. These experiments demonstrate t hat PMNs express COX-2 when appropriately stimulated, Thus, they may a ctively influence the cicosanoid composition of the acute inflammatory milieu.