Macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease

Abstract

Immunohistological techniques using monoclonal antibodies were employed to study the morphology and phenotypic expression of macrophage like cells in ulcerative colitis, Crohn's colitis and histologically normal colonic mucosa. The antibody RFD1 identifies interdigitating (antigen presenting) cells whereas RFD7 binds to mature tissue macrophages. In normal colonic mucosa, the majority of cells recognised by these reagents were positive for Class II antigen expression and a median 87% (range 80-95%) were positive for both RFD1 and RFD7, with 6.5% (ranges 1-14%) positive for either antibody alone. There was much greater macrophage heterogeneity in the ulcerative colitis and Crohn's colitis biopsies than in normal mucosa. Clusters of RFD9+ cells (epithelioid cells) were found in Crohn's colitis and, to a lesser extent, in ulcerative colitis. Some Crohn's colitis sections showed replacement of the normal colonic macrophage phenotype with RFD1-RFD7+ cells (classical scavenger macrophages). The degree of this replacement correlated with the histological severity of the disease. By contrast, large numbers of RFD1+ RFD7- cells, with long dendritic processes, were found in intimate association with the lymphoid infiltrates in the lamina propria of the ulcerative colitis sections. Future studies of the factors controlling macrophage differentiation in tissues may help to explain the greater macrophage heterogeneity in inflammatory bowel disease and the differences between ulcerative colitis and Crohn's colitis observed in this study.