Aberrant mucosal mast cell protease expression in the enteric epithelium of nematode-infected mice lacking the integrin alphavbeta6, a transforming growth factor-beta1 activator.
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.
Knight
Pamela A
PA
Dept. of Veterinary Clinical Studies, Easter Bush Veterinary Centre, The University of Edinburgh, Midlothian EH25 9RG, UK. pam.knight@ed.ac.uk
Brown
Jeremy K
JK
Wright
Steven H
SH
Thornton
Elisabeth M
EM
Pate
Judith A
JA
Miller
Hugh R P
HR
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*
D000951:Antigens, Neoplasm; D016207:Cytokines; D016023:Integrins; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6; D053818:Chymases
Blood. 1999 May 15;93(10):3473-86
10233900
Cytokine. 1999 Apr;11(4):305-12
10328870
Oncogene. 1999 Aug 19;18(33):4734-41
10467421
J Exp Med. 1999 Oct 4;190(7):953-62
10510085
J Cell Mol Med. 2005 Apr-Jun;9(2):421-37
15963261
J Exp Med. 2005 Jun 20;201(12):1961-71
15955837
J Immunol. 2005 Sep 1;175(5):3207-13
16116211
Proteomics. 2006 Jan;6(2):623-31
16342142
J Histochem Cytochem. 2006 Jul;54(7):807-16
16517977
Clin Immunol Immunopathol. 1998 Sep;88(3):287-96
9743616
Clin Exp Allergy. 2002 Feb;32(2):315-24
11929499
Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:115-27
11966532
J Cell Biol. 2002 Apr 29;157(3):493-507
11970960
J Immunol. 2002 Sep 1;169(5):2553-60
12193725
Am J Pathol. 2002 Sep;161(3):771-9
12213704
J Cell Sci. 2003 Jan 15;116(Pt 2):217-24
12482908
Clin Exp Allergy. 2003 Jan;33(1):132-46
12534561
Am J Pathol. 2003 Feb;162(2):597-608
12547717
J Helminthol. 2003 Jun;77(2):155-61
12756069
Blood. 2003 Jun 15;101(12):4725-32
12560232
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7761-6
12796512
Clin Exp Allergy. 2003 Jul;33(7):1005-12
12859460
Blood. 2004 Apr 1;103(7):2655-60
14604954
J Clin Invest. 2004 May;113(9):1364-74
15124028
Am J Pathol. 2004 Jul;165(1):95-106
15215165
Gastroenterology. 2004 Jul;127(1):155-65
15236182
Immunol Rev. 2004 Oct;201:139-55
15361238
Infect Immun. 2004 Oct;72(10):6076-86
15385512
Parasite Immunol. 1983 Jan;5(1):1-12
6687492
J Immunol. 2000 Feb 15;164(4):2046-52
10657657
J Leukoc Biol. 2000 Mar;67(3):350-6
10733095
Infect Immun. 2000 Oct;68(10):5635-44
10992464
J Exp Med. 2000 Dec 18;192(12):1849-56
11120781
Parasite Immunol. 2001 Jan;23(1):39-42
11136476
Gastroenterology. 2001 Mar;120(4):914-24
11231945
Nat Immunol. 2001 May;2(5):436-42
11323698
J Allergy Clin Immunol. 2001 May;107(5):772-80
11344341
Gut. 2001 Aug;49(2):190-8
11454793
Vet Parasitol. 2001 Sep 12;100(1-2):45-50
11522405
Parasite Immunol. 2002 Feb;24(2):67-75
11874561
J Clin Invest. 2002 Apr;109(7):931-7
11927620
Infect Immun. 1983 Jul;41(1):445-7
6345400
Parasitology. 1987;94 Suppl:S77-100
3295692
Ann Allergy. 1987 Nov;59(5 Pt 2):40-3
3479922
J Cell Physiol. 1991 Sep;148(3):362-9
1717495
Mol Biol Cell. 1992 Mar;3(3):349-62
1378327
Parasite Immunol. 1993 Jan;15(1):55-9
7679484
J Histochem Cytochem. 1993 Oct;41(10):1521-7
8245410
J Immunol. 1993 Dec 15;151(12):6670-80
8258684
Parasite Immunol. 1994 Jul;16(7):333-8
7970872
J Exp Med. 1995 Dec 1;182(6):1871-81
7500033
Blood. 1996 Apr 15;87(8):3375-83
8605355
J Cell Biol. 1996 May;133(4):921-8
8666675
Int Immunol. 1996 Apr;8(4):559-67
8671643
J Exp Med. 1996 Jul 1;184(1):271-6
8691142
Vet Immunol Immunopathol. 1996 Nov;54(1-4):331-6
8988878
J Gastroenterol. 1997 Feb;32(1):122-6
9058308
J Immunol. 1997 Jul 1;159(1):117-25
9200446
J Biol Chem. 1997 Nov 14;272(46):29158-66
9360993
Eur J Immunol. 1997 Oct;27(10):2536-40
9368607
J Immunol. 1998 Jun 1;160(11):5537-45
9605158
Cell. 1998 Jun 26;93(7):1159-70
9657149
Am J Pathol. 1998 Aug;153(2):491-504
9708809
Eur J Immunol. 1998 Sep;28(9):2672-84
9754555
Am J Respir Cell Mol Biol. 1998 Oct;19(4):636-42
9761761
Curr Top Microbiol Immunol. 1999;236:113-35
9893358
Cell. 1999 Feb 5;96(3):319-28
10025398
EMBO J. 1999 Mar 1;18(5):1280-91
10064594
Clin Exp Immunol. 1999 Mar;115(3):415-20
10193412