Intestinal uptake of macromolecules. III. Studies on the mechanism by which immunization interferes with antigen uptake

Abstract

The mechanism(s) whereby immunization interferes with the intestinal absorption of macromolecules has been examined. After repeated intraperitoneal injection of protein antigens emulsified in incomplete Freund's adjuvant into rats, everted gut sacs from these animals and controls were exposed to radiolabeled antigen in vitro. There was a significant decrease in absorption of antigen by gut sacs from immunized rats as compared to control rats. On further analysis, it was found that, in contrast to controls, gut sacs from immunized rats showed an increased initial adsorption of labeled antigen. Furthermore, gut sacs from immunized rats showed enhanced breakdown of labeled antigen on prolonged incubation. Following incubation, gut sacs were rinsed and the amount of radioactivity eluted was determined. More radioactivity was present in the first rinse fluid of gut sacs from immunized rats than in rinse fluid from controls. On density gradient ultracentrifugation of the former fluids, radioactivity was localized in the middle or bottom of the gradient, whereas radioactivity in the latter fluids was located at the top of the gradient. The rapidly sedimenting labeled antigen was co-precipitated in the reaction of rabbit anti-rat IgG1 and IgG1 protein, suggesting the presence of antigen-IgG1 antibody complexes in the rinse fluid. These findings suggest that in vitro, antigen becomes rapidly associated with antibodies present on the surface of the gut. Formation of antigen-antibody complexes seems to prevent binding of antigen to and subsquent pinocytosis by the intestinal epithelial cells. Antigen-antibody complexes retained in the muous coat of the gut may be degraded by local proteases. The findings in this study suggest an additional role for antibodies present on mucosal surfaces, i.e., protection against absorption of ingested proteins which have escaped normal digestion in the intestinal lumen.