title: SHP-1 regulation of mast cell function in allergic inflammation and anaphylaxis.
abstract: Allergic inflammation and severe allergic reactions (anaphylaxis) are important in allergen induced diseases. Bacterial products such as lipopolysaccharide (LPS) are ubiquitous and can facilitate allergen induced Th2 immune responses. Phosphatase SHP-1 is critical in regulating immunological homeostasis and in allergen induced Th2 immune responses in the lung. However, the mechanisms underlying the initiation of allergic inflammation and allergen induced anaphylaxis are still not completely elucidated and it is unclear whether SHP-1 plays any role in LPS-induced airway inflammation and in allergen-induced anaphylaxis. In this study we tested the hypothesis that phosphatase SHP-1 plays an important role in allergic inflammation and anaphylaxis and determined whether its effects are through regulation of mast cell functions. SHP-1 deficient (mev/+ and mev/mev) and mast cell deficient (Kit(W-sh)) mice were examined in their responses to LPS airway stimulation and to ovalbumin (OVA) allergen induced systemic anaphylaxis. Compared to wild type mice, mev/+ mice had significantly enhanced LPS induced airway inflammation and OVA induced anaphylactic responses, including hypothermia and clinical symptoms. These changes were mast cell dependent as Kit(W-sh) mice had reduced responses whereas adoptive transfer of mast cells restored the responses. However, T and B cells were not involved and macrophages did not play a significant role in LPS induced airway inflammation. Interestingly, basophil differentiation from SHP-1 deficient bone marrow cells was significantly reduced. These findings provided evidence that through regulation of mast cell functions SHP-1 plays a critical role as a negative regulator in allergic inflammation and in allergen induced anaphylaxis. In addition, SHP-1 seems to be required for normal basophil development.
authors: Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA.
authors: Li
authors: L
authors: Zhou
authors: Sun Young
authors: SY
authors: Oh
authors: Yuqi
authors: Y
authors: Zhou
authors: Baojun
authors: B
authors: Yuan
authors: Fan
authors: F
authors: Wu
authors: Min Hee
authors: MH
authors: Oh
authors: Yefu
authors: Y
authors: Wang
authors: Cliff
authors: C
authors: Takemoto
authors: Nico
authors: N
authors: Van Rooijen
authors: Tao
authors: T
authors: Zheng
authors: Zhou
authors: Z
authors: Zhu
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D008070:Lipopolysaccharides; D010047:Ovalbumin; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse
references: J Neuroimmunol. 2012 May 15;246(1-2):51-7
references: 22458980
references: J Allergy Clin Immunol. 2011 Jun;127(6):1552-61.e1
references: 21624619
references: Lab Invest. 2009 Jul;89(7):742-59
references: 19398961
references: J Exp Med. 2002 Dec 16;196(12):1645-51
references: 12486107
references: J Immunol. 1976 Apr;116(4):936-43
references: 56406
references: Clin Exp Allergy. 2003 Dec;33(12):1711-6
references: 14656359
references: Clin Exp Allergy. 2010 Apr;40(4):536-46
references: 20447074
references: MMWR Suppl. 2011 Jan 14;60(1):84-6
references: 21430629
references: Am J Respir Crit Care Med. 2006 Jan 1;173(1):56-63
references: 16192454
references: J Clin Invest. 1999 Mar;103(6):779-88
references: 10079098
references: N Engl J Med. 2002 Sep 19;347(12):869-77
references: 12239255
references: J Clin Invest. 2002 May;109(10):1351-9
references: 12021251
references: Cell. 1993 Jul 2;73(7):1445-54
references: 8324828
references: Am J Pathol. 2005 Sep;167(3):835-48
references: 16127161
references: Am J Pathol. 1984 Aug;116(2):179-92
references: 6380298
references: J Hered. 1975 Sep-Oct;66(5):250-8
references: 1184950
references: J Immunol. 2007 Nov 15;179(10):6696-703
references: 17982059
references: J Immunol. 2007 Apr 15;178(8):5375-82
references: 17404323
references: J Immunol. 2002 Oct 1;169(7):3801-10
references: 12244175
references: J Clin Invest. 2003 Jan;111(1):109-19
references: 12511594
references: NCHS Data Brief. 2008 Oct;(10):1-8
references: 19389315
references: PLoS One. 2010 Nov 30;5(11):e14174
references: 21151496
references: Annu Rev Immunol. 2007;25:473-523
references: 17291189
references: Immunity. 2008 Apr;28(4):581-9
references: 18342553
references: Gene. 2003 Mar 13;306:1-12
references: 12657462
references: Am J Respir Cell Mol Biol. 2009 May;40(5):568-74
references: 18952567
references: Am J Respir Cell Mol Biol. 2008 Oct;39(4):412-9
references: 18441283
references: Eur Respir J. 2008 Apr;31(4):773-82
references: 18094004
references: J Immunol. 2001 Apr 1;166(7):4391-8
references: 11254693
references: Lab Invest. 2008 Mar;88(3):243-55
references: 18209728
references: N Engl J Med. 2002 May 30;346(22):1699-705
references: 12037149
references: Am J Physiol Lung Cell Mol Physiol. 2008 Aug;295(2):L314-25
references: 18556802
references: J Immunol. 2010 Feb 1;184(3):1180-90
references: 20042576
references: J Clin Invest. 2005 Feb;115(2):459-67
references: 15650773
references: Biochem Biophys Res Commun. 2010 Feb 26;393(1):137-43
references: 20117097
references: Semin Immunol. 2000 Aug;12(4):361-78
references: 10995583
references: J Cell Physiol. 2007 Oct;213(1):126-36
references: 17458900