Inflammatory agonists induce cyclooxygenase type 2 expression by human neutrophils

Christopher G. Maloney, William A. Kutchera, Kurt H. Albertine, Thomas M. McIntyre, Stephen M. Prescott, Guy A. Zimmerman

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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 tune- and concentration-dependent fashion when isolated human PMNs were exposed to LPS; COX-2 was also induced, or its expression was increased, by TNF-α, 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.

Original languageEnglish (US)
Pages (from-to)1402-1410
Number of pages9
JournalJournal of Immunology
Volume160
Issue number3
StatePublished - Feb 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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