BASAL SECRETION AND ANAPHYLACTIC RELEASE OF RAT MAST-CELL PROTEASE-II (RMCP-II) FROM EX-VIVO PERFUSED RAT JEJUNUM - TRANSLOCATION OF RMCP-II INTO THE GUT LUMEN AND ITS RELATION TO MUCOSAL HISTOLOGY

The kinetics of the release of rat mast cell protease-II (RMCP-II) from mucosal mast cells in the jejunum of Nippostrongylus brasiliensis primed (immune) rats was investigated using ex vivo perfusion of a segment of jejunum through the cranial mesenteric artery. The aim of the study was to assess the role of the protease in anaphylaxis and in particular to ascertain whether it is responsible for the histological changes, which include widespread epithelial shedding, seen ire the mucosa in in vivo models of anaphylaxis. Perfusion of the jejunal vasculature with a Krebs-Ringer buffer showed that there was basal secretion of RMCP-II by jejunal mast cells in all rats studied. The baseline concentration of RMCP-II was significantly greater (p<0.05) in immune rats (>7 ng/ml) exposed to nippostrongylus infection than in control, naive animals (<2 ng/ml). Challenge of immune rats with 100 or 400 worm equivalents of whole worm antigen resulted in an immediate (within 40 seconds) and significant (p<0.02) increase in the concentration of RMCP-II (to >3 mu g/ml) in the vascular perfusate, which was not seen in naive rats or immune rats challenged with an irrelevant antigen. Greater amounts of RMCP-II were also recovered from the jejunal lumen of immune rats compared with naive rats after challenge of both groups with worm antigen. Despite the release of microgram quantities of RMCP-II into the gut lumen and vascular perfusate, however, there were no significant changes seen in the mucosal histology. These results suggest that RMCP-II alone is not responsible for the loss of gut epithelium seen during anaphylaxis in the rat.