Delayed expulsion of the nematode Trichinella spiralis in mice lacking themucosal mast cell-specific granule chymase, mouse mast cell protease-1

Expulsion of gastrointestinal nematodes is associated with pronounced mucos al mast cell (MMC) hyperplasia, differentiation, and activation, accompanie d by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The beta -chymase mouse mast cell protease-1 (mMCP-1) is expre ssed predominantly by intraepithelial MMCs, and levels in the bloodstream a nd intestinal lumen are maximal at the time of worm expulsion in parasitize d mice. To address the in vivo functions of MMC-specific beta -chymases, we have generated transgenic mice chat lack the mMCP-1 gene. They were backcr ossed onto a congenic BALB/c background to investigate the response to nema tode infection. The deletion of the mMCP-1 gene is associated with signific antly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were alt ered in Nippostrongylus-infected mMCP-1(-/-) BALB/c mice. These data demons trate for the first time, that the ablation of an MMC-derived effector mole cule compromises the expulsion process.