title: Aberrant mucosal mast cell protease expression in the enteric epithelium of nematode-infected mice lacking the integrin alphavbeta6, a transforming growth factor-beta1 activator.
abstract: Infection of mice with the nematode Trichinella spiralis triggers recruitment and differentiation of intraepithelial intestinal mucosal mast cells expressing mouse mast cell protease 1 (Mcpt-1), which contributes to expulsion of the parasite. Expression of Mcpt-1 is transforming growth factor (TGF)-beta1-dependent in vitro. TGF-beta1, which is secreted within tissues as a biologically inactive complex with latency-associated peptide, requires extracellular modification to become functionally active. The integrin-alpha(nu)beta(6) mediates local activation of TGF-beta(1) in association with epithelia. Using T. spiralis-infected beta(6)(-/-) mice, we show accumulation of mucosal mast cells in the lamina propria of the small intestine with minimal recruitment into the epithelial compartment. This was accompanied by a coordinate reduction in expression of both Mcpt-1 and -2 in the jejunum and increased tryptase expression, whereas Mcpt-9 became completely undetectable. In contrast, the cytokine stem cell factor, a regulator of mast cell differentiation and survival, was significantly up-regulated in T. spiralis-infected beta(6)(-/-) mice compared with infected beta(6)(+/+) controls. Despite these changes, beta(6)(-/-) mice still appeared to expel the worms normally. We postulate that compromised TGF-beta(1) activation within the gastrointestinal epithelial compartment is a major, but not the only, contributing factor to the observed changes in mucosal mast cell protease and epithelial cytokine expression in beta(6)(-/-) mice.
authors: Dept. of Veterinary Clinical Studies, Easter Bush Veterinary Centre, The University of Edinburgh, Midlothian EH25 9RG, UK. pam.knight@ed.ac.uk
authors: Pamela A
authors: PA
authors: Knight
authors: Jeremy K
authors: JK
authors: Brown
authors: Steven H
authors: SH
authors: Wright
authors: Elisabeth M
authors: EM
authors: Thornton
authors: Judith A
authors: JA
authors: Pate
authors: Hugh R P
authors: HR
authors: Miller
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D001853:Bone Marrow / Q000276:immunology; D053818:Chymases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004423:Ear; D016023:Integrins / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology*; D007583:Jejunum / Q000276:immunology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D013270:Stomach / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D016023:Integrins; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6; D053818:Chymases
references: Blood. 1999 May 15;93(10):3473-86
references: 10233900
references: Cytokine. 1999 Apr;11(4):305-12
references: 10328870
references: Oncogene. 1999 Aug 19;18(33):4734-41
references: 10467421
references: J Exp Med. 1999 Oct 4;190(7):953-62
references: 10510085
references: J Cell Mol Med. 2005 Apr-Jun;9(2):421-37
references: 15963261
references: J Exp Med. 2005 Jun 20;201(12):1961-71
references: 15955837
references: J Immunol. 2005 Sep 1;175(5):3207-13
references: 16116211
references: Proteomics. 2006 Jan;6(2):623-31
references: 16342142
references: J Histochem Cytochem. 2006 Jul;54(7):807-16
references: 16517977
references: Clin Immunol Immunopathol. 1998 Sep;88(3):287-96
references: 9743616
references: Clin Exp Allergy. 2002 Feb;32(2):315-24
references: 11929499
references: Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:115-27
references: 11966532
references: J Cell Biol. 2002 Apr 29;157(3):493-507
references: 11970960
references: J Immunol. 2002 Sep 1;169(5):2553-60
references: 12193725
references: Am J Pathol. 2002 Sep;161(3):771-9
references: 12213704
references: J Cell Sci. 2003 Jan 15;116(Pt 2):217-24
references: 12482908
references: Clin Exp Allergy. 2003 Jan;33(1):132-46
references: 12534561
references: Am J Pathol. 2003 Feb;162(2):597-608
references: 12547717
references: J Helminthol. 2003 Jun;77(2):155-61
references: 12756069
references: Blood. 2003 Jun 15;101(12):4725-32
references: 12560232
references: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7761-6
references: 12796512
references: Clin Exp Allergy. 2003 Jul;33(7):1005-12
references: 12859460
references: Blood. 2004 Apr 1;103(7):2655-60
references: 14604954
references: J Clin Invest. 2004 May;113(9):1364-74
references: 15124028
references: Am J Pathol. 2004 Jul;165(1):95-106
references: 15215165
references: Gastroenterology. 2004 Jul;127(1):155-65
references: 15236182
references: Immunol Rev. 2004 Oct;201:139-55
references: 15361238
references: Infect Immun. 2004 Oct;72(10):6076-86
references: 15385512
references: Parasite Immunol. 1983 Jan;5(1):1-12
references: 6687492
references: J Immunol. 2000 Feb 15;164(4):2046-52
references: 10657657
references: J Leukoc Biol. 2000 Mar;67(3):350-6
references: 10733095
references: Infect Immun. 2000 Oct;68(10):5635-44
references: 10992464
references: J Exp Med. 2000 Dec 18;192(12):1849-56
references: 11120781
references: Parasite Immunol. 2001 Jan;23(1):39-42
references: 11136476
references: Gastroenterology. 2001 Mar;120(4):914-24
references: 11231945
references: Nat Immunol. 2001 May;2(5):436-42
references: 11323698
references: J Allergy Clin Immunol. 2001 May;107(5):772-80
references: 11344341
references: Gut. 2001 Aug;49(2):190-8
references: 11454793
references: Vet Parasitol. 2001 Sep 12;100(1-2):45-50
references: 11522405
references: Parasite Immunol. 2002 Feb;24(2):67-75
references: 11874561
references: J Clin Invest. 2002 Apr;109(7):931-7
references: 11927620
references: Infect Immun. 1983 Jul;41(1):445-7
references: 6345400
references: Parasitology. 1987;94 Suppl:S77-100
references: 3295692
references: Ann Allergy. 1987 Nov;59(5 Pt 2):40-3
references: 3479922
references: J Cell Physiol. 1991 Sep;148(3):362-9
references: 1717495
references: Mol Biol Cell. 1992 Mar;3(3):349-62
references: 1378327
references: Parasite Immunol. 1993 Jan;15(1):55-9
references: 7679484
references: J Histochem Cytochem. 1993 Oct;41(10):1521-7
references: 8245410
references: J Immunol. 1993 Dec 15;151(12):6670-80
references: 8258684
references: Parasite Immunol. 1994 Jul;16(7):333-8
references: 7970872
references: J Exp Med. 1995 Dec 1;182(6):1871-81
references: 7500033
references: Blood. 1996 Apr 15;87(8):3375-83
references: 8605355
references: J Cell Biol. 1996 May;133(4):921-8
references: 8666675
references: Int Immunol. 1996 Apr;8(4):559-67
references: 8671643
references: J Exp Med. 1996 Jul 1;184(1):271-6
references: 8691142
references: Vet Immunol Immunopathol. 1996 Nov;54(1-4):331-6
references: 8988878
references: J Gastroenterol. 1997 Feb;32(1):122-6
references: 9058308
references: J Immunol. 1997 Jul 1;159(1):117-25
references: 9200446
references: J Biol Chem. 1997 Nov 14;272(46):29158-66
references: 9360993
references: Eur J Immunol. 1997 Oct;27(10):2536-40
references: 9368607
references: J Immunol. 1998 Jun 1;160(11):5537-45
references: 9605158
references: Cell. 1998 Jun 26;93(7):1159-70
references: 9657149
references: Am J Pathol. 1998 Aug;153(2):491-504
references: 9708809
references: Eur J Immunol. 1998 Sep;28(9):2672-84
references: 9754555
references: Am J Respir Cell Mol Biol. 1998 Oct;19(4):636-42
references: 9761761
references: Curr Top Microbiol Immunol. 1999;236:113-35
references: 9893358
references: Cell. 1999 Feb 5;96(3):319-28
references: 10025398
references: EMBO J. 1999 Mar 1;18(5):1280-91
references: 10064594
references: Clin Exp Immunol. 1999 Mar;115(3):415-20
references: 10193412