Constitutive expression of mouse mast cell protease-1 in normal BALB/c mice and its up-regulation during intestinal nematode infection.
Rodent intestinal mucosal mast cells (IMMC) store and secrete soluble granule serine proteases, the beta-chymases, which may promote epithelial permeability during intestinal hypersensitivity reactions. The beta-chymase mouse mast cell protease-1 (mMCP-1) is generally considered to be expressed late in the in vitro differentiation of mast cells. The purpose of this study was to determine the kinetics of mMCP-1 transcription and expression in vivo during nematode-induced IMMC hyperplasia. Concentrations of mMCP-1 in blood and jejunum of BALB/c mice were quantified by enzyme-linked immunosorbent assay before and at various stages after infection with the intestinal nematode Nippostronglyus brasilliensis. Mature mMCP-1 enzyme was detected in jejunal homogenate (194 ng/mg soluble protein) and in blood (8.3 ng/ml serum) from normal uninfected BALB/c mice. Maximal IMMC hyperplasia occurred 7-14 days post infection and was significantly correlated with increased levels of mMCP-1 in jejunum (r = 0.58, P < 0.001) and with raised concentrations of mMCP-1 in serum (r = 0.66, P < 0.001). Transcription of the mMCP-1 gene was detected by RNA blotting in normal, uninfected jejunum, but transcription was up-regulated after infection with maximal transcription occurring on days 7 and 14. In conclusion, mMCP-1 transcription, storage and secretion occur constitutively in normal BALB/c jejunum but this basal secretion is up-regulated during nematode infection, suggesting both a physiological and pathological function for this protease.
Wastling
J M
JM
Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, UK.
Scudamore
C L
CL
Thornton
E M
EM
Newlands
G F
GF
Miller
H R
HR
D000818:Animals; D015152:Blotting, Northern; D053818:Chymases; D007413:Intestinal Mucosa / Q000201:enzymology; D007583:Jejunum / Q000201:enzymology; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus; D012697:Serine Endopeptidases / Q000378:metabolism*; D017206:Strongylida Infections / Q000201:enzymology*; D015854:Up-Regulation
D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse