title: Inflammatory agonists induce cyclooxygenase type 2 expression by human neutrophils.
abstract: The synthesis of prostanoids is regulated by cyclooxygenases (prostaglandin H synthases), which catalyze the conversion of arachidonic acid to PGH2. Cyclooxygenases are the target of aspirin and other nonsteroidal anti-inflammatory agents. In this study, we found that human polymorphonuclear leukocytes (PMNs) express the inducible isoform of cyclooxygenase, COX-2, when stimulated by LPS whereas the protein was not detectable in freshly isolated human PMNs. We also found by immunohistochemical analysis that COX-2 is expressed in PMNs in inflamed human tissues. COX-2 was induced in a time- and concentration-dependent fashion when isolated human PMNs were exposed to LPS; COX-2 was also induced, or its expression was increased, by TNF-alpha, IL-1, and IL-8. Expression of COX-2 in stimulated PMNs was paralleled by secretion of PGE2. The release of PGE2 was blocked by a selective nonsteroidal inhibitor of COX-2, indicating that the enzyme is responsible for the prostanoids produced, and was inhibited by dexamethasone. The time course of LPS-induced COX-2 expression and other features were different in freshly 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 little effect on this response by PMNs. These experiments demonstrate that PMNs express COX-2 when appropriately stimulated. Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.
authors.affiliation: The Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City 84112, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Maloney
authors.forename: W A
authors.initials: WA
authors.lastname: Kutchera
authors.forename: K H
authors.initials: KH
authors.lastname: Albertine
authors.forename: T M
authors.initials: TM
authors.lastname: McIntyre
authors.forename: S M
authors.initials: SM
authors.lastname: Prescott
authors.forename: G A
authors.initials: GA
authors.lastname: Zimmerman
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000201:enzymology; D018925:Chemokines / Q000819:agonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000819:agonists; D004790:Enzyme Induction / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000819:agonists*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D018925:Chemokines; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011451:Prostaglandin-Endoperoxide Synthases