MACROMOLECULAR TRANSPORT BY RAT GASTRIC-MUCOSA

We previously demonstrated that the stomach is capable of mounting a type I hypersensitivity reaction to luminal antigen challenge. These findings imply that antigenically intact macromolecules cross the gastric mucosa. To test this hypothesis, rat gastric mucosa was mounted in Ussing chambers, and bovine serum albumin (BSA, 0.5 mg/ml) and I-125-labeled BSA (10-mu-Ci) were added to mucosal fluids. After equilibration, serosal fluids were sampled for two 30-min periods, and fluxes of immunologically intact BSA (determined by an enzyme-linked immunosorbent assay) and total BSA (I-125-BSA) were calculated under basal conditions and in the presence of NaF and colchicine, and at 4-degrees-C. Additional experiments examined macromolecular permeability in sensitized-challenged tissues. Immunologically intact BSA (21.3 +/- 4.5 ng . 30 min-1 . cm-2) crossed the gastric mucosa as approximately one-fourth of the total BSA flux (78.2 +/- 7.5 ng . 30 min-1 . cm-2). The uptake of immunologically intact BSA was significantly reduced by NaF, an inhibitor of ATP production and endocytosis; colchicine, which inhibits polymerization of cytoskeletal microtubules; and at 4-degrees-C, a general metabolic inhibitor. The transmural passage of antigen was not significantly altered by immunoglobulin E-mediated anaphylaxis. These findings indicate that intact protein antigens cross the gastric mucosa by an active, energy-dependent mechanism that uses the microtubular network.