Mucosal synthesis and release of prostaglandin E2 from activated eosinophils and macrophages in ulcerative colitis.

Abstract

To study the synthesis and release of prostaglandin E2 (PGE2) in diseased and healthy areas of the colon in ulcerative colitis/proctitis (UC) patients. Perfusate fluid from rectal and sigmoid segments in patients with UC was analyzed for PGE2, eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha concentrations. To further elucidate the cell-specific origin of mucosal PGE2 synthesis, double immunofluorescence staining as well as imaging analysis using antibodies reactive with prostaglandin H-synthase and cell-specific antigens were used on surgical colonic specimens from patients with active UC and from controls. The concentrations of PGE2 were, on average, 10-fold higher in perfusates from diseased areas in patients with UC than in perfusates from healthy areas in patients and controls. The PGE2 values correlated well with the released concentrations of eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha. In the tissue specimens, there was a prominent colocalization in the expression of prostaglandin H-synthase on the one hand and CD 68 (a macrophage marker) and EG1/EG2 (eosinophil cationic protein markers) on the other hand, in both UC patients and controls. This did not apply to prostaglandin H-synthase and antibodies against B and T lymphocytes, neutrophils, or epithelial cells. The increased PGE2 production found in the inflamed mucosa in active UC may be caused by a fraction of activated eosinophils and macrophages.