LONG-TERM ANTIGEN CHALLENGE RESULTS IN PROGRESSIVELY DIMINISHED MUCOSAL MAST-CELL DEGRANULATION IN RATS

Background & Aims: The effects of short-term antigenic activation of m ast cells on the gastrointestinal tract have been well characterized, but little is known about the effects of long-term exposure to antigen on mucosal mast cell reactivity, The aim of this study was to determi ne the effects of long-term antigen exposure on mucosal mast cell reac tivity in the gastrointestinal mucosa, Methods: Rats sensitized to chi cken ovalbumin were orally challenged (short-term or long-term) with a ntigen. Rat mast cell protease II (RMCP-II) content was measured in se rum as an index of mucosal mast cell degranulation. Results: Short-ter m oral antigen challenge caused a 30-fold increase in serum RMCP-II le vels, RMCP-II release was markedly diminished in long term-challenged rats (P < 0.001), despite increased tissue RMCP-II levels in stomach a nd jejunum, Although short-term antigen challenge significantly increa sed gastric acid secretion, no such response was observed after the lo ng-term antigen challenge, In rats undergoing long-term challenge, a s ignificant release of RMCP-II in response to intravenous antigen was n ot observed; however, mucosal mast cells remained responsive to intrav enous anti-immunoglobulin E. Conclusions: Repeated activation of mucos al mast cells results in a progressive diminution of RMCP-II release n ot attributable to depletion of this mediator. This may represent an a daptive response aimed at minimizing the potentially deleterious effec ts of repeated exposure to an antigen.