The synthesis of prostanoids is regulated by prostaglandin H synthases (PHS) (cyclooxy genäse), catalyzing the conversion of arachidonic acid to PGH2- PHS is the target of aspirin and other nonsteroidal anti-inflammatory agents. An inducible form, PHS-2, has recently been identified. It differs from Ihe constitutive form, PHS-1, in sequence, inhibition by anti-inflammatory agenis, cell distribution and other features. We report for the first time that human polymorphonuclear leukocytes (PMNs) express PHS-2 when stimulated by lipopolysaccharide (LPS). By Western analysis, PHS-2 was not detectable in freshly-isolated human PMNs. Levels of the protein increased in a time- and concentration-dependent fashion when PMNs were exposed to LPS. Expression of PHS-2 was paralleled by secretion of prostaglandin E2, suggesting that the enzyme influences the prostanoids produced by these cells. Human monocytes, monocytic cell lines, and human monocyte-derived macrophages also expressed PHS-2 when stimulated with LPS. The time course of LPS induced PHS-2 was different between freshly-isolated PMNs and mor/>,ytes: in PMNs, levels peaked !it 3 hr. and returned to baseline by 18 hr., whereas levels continuously increased in monocytes over a 24 hr. period. The time course in stimulated macrophages differed from that in both PMNs and monocytes, indicating that PHS-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, interleukin (IL)-IO, which has been reponed to suppress LPS induced PHS-2 expression in monocytes, had no effect on LPS induced PHS-2 expression in PMNs. The level of PHS-2 in LPS-stimulated PMNs was enhanced by treatment of the cells wiih tumor necrosis factor-a, IL-8, and IL-1B, These experiments show that PMNs, a cell thought to have little or no protein synthetic potential until recently, express PHS-2, Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|Publication status||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)