Production of prostaglandin D 2 by murine macrophage cell lines

Abstract

Several tumor-derived murine macrophage cell lines were evaluated in vitro as cloned prototypes of tissue macrophages for their ability to metabolize arachidonic acid. Unexpectedly, two cell lines, J774A.1 and WR19M.1, rapidly converted exogenous 14C-arachidonic acid (AA) to a single major prostaglandin metabolite. The compound, PGD 2, was positively identified by TLC, HPLC, and GC-MS. The enzymatic formation of the PGD 2 was shown by inhibition of its formation by indomethacin and reduced formation of 14C-PGD 2 and 14C-PGD 2 in boiled cells. When J774A.1 cells were prelabeled with 3H-AA, cultured for 24 hours, and stimulated with lipopolysaccharide (LPS), PGD 2 was again the predominant product. No other tumor derived cell lines, including several other murine macrophage lines, produced significant amounts of PGD 2. Elicited and activated murine peritoneal macrophages produced only small amounts of PGD 2, but resident peritoneal macrophages produced modest amounts of PGD 2. Exaggerated formation of PGD 2 by J774A.1 and WR19M.1 cells may be a consequence of neoplastic transformation or the clonal expansion of a minor subpopulation of normal tissue macrophages.