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^a Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, and Wellcome Trust Centre for Research in Comparative Respiratory Medicine, University of Edinburgh, Easter Bush Veterinary Centre, Midlothian EH25 9RG, United Kingdom
^b Department of Immunology, Strathclyde Institute of Biological Sciences, Glasgow G4 ONR, United Kingdom
Dept. of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK.44-31-650-769744-31-650-7698

pam.knight{at}vet.ed.ac.uk

Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The β-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific β-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly 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 altered in Nippostrongylus-infected mMCP-1^–/– BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.

Key Words: mucosal immunity • mast cell hyperplasia • helminth parasite • submucosa • Nippostrongylus brasiliensis

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