Mechanism of antigen absorption from the small intestine

Abstract

Evidence exists that the intestine is permeable to antigenic macromolecules. The mechanism of absorption and factors affecting antigen uptake are largely unknown. Studies relating molecular size to the clearance of macromolecules from intestinal loops suggest a diffusion phenomenon. However, the uptake of horseradish peroxidase and fluorescent-labelled gamma globulin by epithelial cells is affected by metabolic inhibitors suggesting an energy-dependent process. To clarify mechanisms of antigen absorption the uptake of horseradish peroxidase (HRP) (M.W. 40,000) and two C14-dextrans (M.W. 15,000 and 60,000) were studied in rat everted gut sac preparations. Electron micrographs showed that HRP progressed from membrane-bound structures within epithelial cells into the intercellular space and finally into the lamina propria. Absorption of HRP was five times greater in the jejunum than in the ileum and jejunal uptake was inhibited by S-13, an uncoupling agent. Large weight dextran was absorbed at three times the rate of small weight dextran at equivalent concentrations. Experiments performed at 0° or under nitrogen reduced the absorption of the large weight dextran to that seen with smaller weight dextrans. These studies suggest that the uptake of some antigens occurs by an energy-dependent pinocytotic mechanism. The uptake appears to be greater in the jejunum than the ileum and the jejunal absorption shows a more marked energy-dependency. The energy dependent uptake of the larger dextran suggests a mechanism for absorption of macromolecules other than diffusion. (Work supported by grants from The John A. Hartford Foundation, Inc.)