Prostanoids in human colonic mucosa: Effects of inflammation on PGE(2) receptor expression

Although the tissue concentration of PGE(2) is heightened 3-fold or more du ring mucosal inflammation the cellular targets of prostanoids in human muco sa and the resulting changes in cell physiology have not been fully explore d. We used a panel of immunoglobulin and mRNA probes in order to localize a nd quantitate che four member EP family of prostanoid receptors for binding PGE(2) to cells of histologically normal and inflamed human colonic mucose , and then examined prostanoid-induced changes in mucosal lymphocyte functi on. Prostanoid receptors were selectively expressed on a limited number of human colonic mucosal cells; EP4 alone was expressed on lamina propria mono nuclear cells. Dual immunostaining in situ identified the CD3(+) T lymphocy te as a major EP4 receptor-bearing cell in normal mucosa. Flow cytometry of isolated cells showed that 19.2% of lamina propria mononuclear cells were EP4+, and almost 30% of these were CD3(+). In situ hybridization with digox ygenin-labeled RNA probes largely confirmed this localization. During infla mmation, mucosal T lymphocytes showed a significant enhancement in EP4 immu noreactive receptor protein. Computer-assisted densitometry of single cells demonstrated an increase in fluorescence intensity from 4.8 +/- 1.8 to 8.6 +/- 1.8 (p < 0.04). The effects of PGE(2) included a 35% reduction in T ly mphocyte IL-2 secretion. COX 1(+) lamina propria cells nearly doubled in nu mber during inflammation; expressed a T lymphocyte marker; but retained an unchanged quantity of immunoreactive COX 1 protein per cell. The number of newly appeared COX 2(+) lymphocytes remained <50% that of COX 1(+) cells. A major perturbation in the number and distribution of PGE(2) receptors and enzymes for prostanoid synthesis occurs in chronic inflammation of the colo n, with consequences for mucosal T lymphocyte function. Human Immunology, 6 1, 684-696 (2000). (C) American Society for Histocompatibility and Immunoge netics, 2000. Published by Elsevier Science Inc.