Inflammatory agonists induce cyclooxygenase type 2 expression by human neutrophils

J Immunol. 1998 Feb 1;160(3):1402-10.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bone Marrow Cells / enzymology
  • Chemokines / agonists
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytokines / agonists
  • Enzyme Induction / drug effects
  • Enzyme Induction / immunology
  • Humans
  • Inflammation Mediators / agonists*
  • Lipopolysaccharides / pharmacology
  • Lung / enzymology
  • Lung / pathology
  • Neutrophil Activation / drug effects
  • Neutrophils / enzymology*
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / metabolism


  • Chemokines
  • Cyclooxygenase Inhibitors
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Prostaglandin-Endoperoxide Synthases