Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1.
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 beta-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 beta-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.
Knight
P A
PA
Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Midlothian EH25 9RG, United Kingdom. pam.knight@vet.ed.ac.uk
Wright
S H
SH
Lawrence
C E
CE
Paterson
Y Y
YY
Miller
H R
HR
D000818:Animals; D053818:Chymases; D017353:Gene Deletion; D006651:Histocytochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D007583:Jejunum / Q000276:immunology / Q000469:parasitology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009132:Muscles / Q000469:parasitology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017160:Trichinella spiralis / Q000276:immunology* / Q000502:physiology; D014235:Trichinellosis / Q000276:immunology* / Q000469:parasitology
D012333:RNA, Messenger; D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse