RAPID TRANSEPITHELIAL ANTIGEN TRANSPORT IN RAT JEJUNUM - IMPACT OF SENSITIZATION AND THE HYPERSENSITIVITY REACTION

Background & Aims: Intestine from sensitized rats develops a rapid sec retory response to luminal antigen challenge that depends on activatio n of subepithelial mast cells. The aim of this study was to determine the timing and route of the transepithelial protein antigen transport. Methods: Rats were sensitized to horseradish peroxidase (HRP). After 10-14 days, jejunal segments were resected, mounted in Ussing chambers , and challenged with HRP on the luminal side. Results: Electron micro scopy of tissue specimens fixed at 2 minutes (before mast cell activat ion) showed enhanced endocytic uptake of HRP in enterocytes of HRP-sen sitized rats compared with ovalbumin-sensitized or saline-injected con trols. At this time, HRP was distributed throughout epithelial cells a nd was already evident in the lamina propria. In contrast, HRP was res tricted to the apical region of enterocytes in controls. At 30 minutes (after mast cell activation), in HRP-sensitized rats only, HRP was al so located within tight junctions and the paracellular region between epithelial cells. Tissue conductance was increased in HRP-sensitized r ats beginning 30 minutes after HRP addition and correlated with the ov erall flux of HRP across the tissue. Conclusions: The results show tha t specific sensitization enhances the initial uptake and transcytosis of antigen across intestinal epithelium. Subsequent to activation of m ast cells, antigen transport is further enhanced by penetration throug h the paracellular pathway.