ENDOTHELIAL PROLIFERATION IN EXPERIMENTAL GRANULOMATOUS COLITIS - AUTORADIOGRAPHY AND IMMUNOHISTOCHEMISTRY STUDIES

The time sequence and magnitude of endothelial cell proliferation was investigated in an experimental model of granulomatous colitis in rats , induced by intramural inoculations of mycobacterium Bacillus Calmett e-Guerin. Colonic tissues were assessed by gross examination, histopat hology, autoradiography, and immunohistochemistry. Gross examination o f the colonic tissue showed thickening of the colonic wall, erythema, hemorrhage, and scattered ulcers. Histopathological findings were char acterized by an acute transmural inflammation, progressing to chronic inflammation accompanied by regenerative changes in the glandular epit helium, goblet cell depletion, mucosal atrophy and fibrosis. Well-deve loped noncaseating granulomas were first observed at day 5 and were fo und to be a dominant feature up to day 17. Autoradiographic studies sh owed increased endothelial cell labeling up to 17% at 48 hr, compared to less than 1% labeling in control animals. Immunostaining for factor VIII-related antibody, art endothelial cell marker, showed increased numbers of microvessels and individual positive cells located in areas of inflammation as early as 24 hr. At day 5 these individual cells al ong with dilated neocapillaries were found surrounding the granulomas. This model of granulomatous colitis mimics many features of the human disease state. The early increase in endothelial cell proliferation t hat precedes granuloma formation during the course of the inflammatory response may suggest that the events leading to the expression of gra nulomatous colitis are dependent on endothelial proliferation.