Chapter 4 - Radiation-associated changes in the jejunum of rhesus macaques

Abstract

The immediate radiation-associated injury to the jejunum was largely related to effects on mitotically active cells in the intestinal crypts. Histologic changes consisted of epithelial cell depletion with atrophy and blunting/fusion of villi. The damaged and newly regenerated mucosa had a marked reduction in goblet cells, which would reduce the level of protective mucin on the luminal surface. The radiation-damaged surface epithelial cells had a striking reduction in the CD13+ brush border, indicating a loss of enzymatic activities of the surface epithelium. There was a striking reduction in the Paneth cell population in mucosal crypts and an associated reduction in connective tissue growth factor production by Paneth cells. Repair of the mucosal injury, which commenced within a few days of irradiation, consisted of expansion of the Ki-67+ crypt epithelial cell population and increased expression of Lgr5 in crypt epithelial cells. The intestinal mucosa of many animals was not restored to completely normal histologic structure by the end of the 180-day observation period. Despite the evidence of extensive mucosal injury, immunohistochemical staining for lipopolysaccharide core antigen revealed little microbial penetration through the mucosa. Inflammatory cell infiltration was not a prominent feature of the radiation-associated intestinal injury. Immunohistochemical staining for CD38 revealed no increase in macrophage populations but staining for CD163 revealed a marked increase in CD163+ cells, suggesting a radiation-associated phenotypic shift to a profibrotic macrophage population. Multifocal fibrosis was noted in the jejunal submucosa and serosa, with less pronounced fibrotic changes in the mucosa.