Intestinal epithelial membrane changes in rats immune to Trichinella spiralis

Abstract

Establishment of Trichinella spiralis infective larvae is blocked to a large degree in the immune rat as compared with the nonimmune host. The rapidity with which this response occurs indicates that most worms are either prevented from penetrating the intestinal epithelium or are rejected immediately after cell entry. It is proposed that interference with larval infectivity is due to alterations in the epithelial cell apical or brush border membrane. Alterations may result from prior infection or may reflect an acute change induced by challenge infection. In either case the establishment of normal populations of larvae in the mucosa is disturbed. Lectin binding capacity of brush border membranes was used to assess possible membrane alterations. This parameter in uninfected (control) rats was compared with that in infected rats, which acquire resistance to subsequent challenge, and in infected rats immediately after a challenge inoculum. Enriched brush border membrane preparations were characterized for their binding of wheat germ agglutinin, which attaches specifically to the carbohydrate, N-acetylglucosamine. Maximum specific binding of 125I-labeled wheat germ agglutinin occurred within 20 min. The spontaneous rate of dissociation was negligible for 90 min. Highest specific binding resulted at 24°C, pH 6.0 and with 75 μg bursh border membrane protein per assay tube. Results suggested the existence of multiple binding sites. 1 mg of membrane protein from uninfected rats and rats immunized by primary infection maximally bound 9.8 × 10 10 and 4.3 × 10 10 molecules of wheat germ agglutinin, respectively. Binding for the ‘immune’ brush border membrane, as compared with the ‘uninfected’ brush border membrane was reduced during the first 3 weeks of infection and remained low for at least 3 months. No further reduction in binding was observed for brush border membrane isolated within minutes after a secondary infection. These results reveal the induction by a primary infection of changes in brush border membrane structure and the persistance of these changes in the immune host. In view of the rapid turnover time of epithelial tissue the mechanism by which this change is perpetuated speculatively involves immune elements in the lamina propria.