Increased density of intraepithelial mast cells in patients with exercise-induced bronchoconstriction regulated through epithelially derived thymic stromal lymphopoietin and IL-33

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:133

Article

Lai, Ying¹  Altemeier, William A.¹  Vandree, John¹  Piliponsky, Adrian M.⁶  Johnson, Brian⁵  Appel, Cara L.⁵  Frevert, Charles W.⁵  Hyde, Dallas M.⁷  Ziegler, Steven F.⁸  Smith, Dirk E.⁹  Henderson, William R., Jr.²  Gelb, Michael H.^3,4  Hallstrand, Teal S.¹ 

[1] Univ Washington, Dept Med, Div Pulm & Crit Care, Seattle, WA 98195 USA

[2] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[3] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA

[6] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA

[7] Univ Calif Davis, Sch Vet Med, Davis, CA USA

[8] Benaroya Res Inst, Program Immunol, Seattle, WA USA

[9] Amgen Inc, Dept Inflammat Res, Seattle, WA USA

关键词: Asthma;    airway hyperresponsiveness;    eicosanoid;    epithelial cell;    leukotriene;   

DOI  :  10.1016/j.jaci.2013.08.052

来源: Elsevier

【 摘 要 】

Background: Exercise-induced bronchoconstriction (EIB) is a prototypical feature of indirect airway hyperresponsiveness. Mast cells are implicated in EIB, but the characteristics, regulation, and function of mast cells in patients with EIB are poorly understood. Objectives: We sought to examine mast cell infiltration of the airway epithelium in patients with EIB and the regulation of mast cell phenotype and function by epithelially derived cytokines. Methods: Endobronchial biopsy specimens, epithelial brushings, and induced sputum were obtained from asthmatic patients with and without EIB and healthy control subjects. Mast cell proteases were quantified by using quantitative PCR, and mast cell density was quantified by using design-based stereology. Airway epithelial responses to wounding and osmotic stress were assessed in primary airway epithelial cells and ex vivo murine lung tissue. Mast cell granule development and function were examined in cord blood-derived mast cells. Results: Tryptase and carboxypeptidase A3 expression in epithelial brushings and epithelial mast cell density were selectively increased in the asthma group with EIB. An in vitro scratch wound initiated the release of thymic stromal lymphopoietin, which was greater in epithelial cells derived from asthmatic patients. Osmotic stress induced the release of IL-33 from explanted murine lungs, which was increased in allergen-treated mice. Thymic stromal lymphopoietin combined with IL-33 increased tryptase and carboxypeptidase A3 immunostaining in mast cell precursors and selectively increased cysteinyl leukotriene formation by mast cells in a manner that was independent of in vitro sensitization. Conclusions: Mast cell infiltration of the epithelium is a critical determinant of indirect airway hyperresponsiveness, and the airway epithelium might serve as an important regulator of thedevelopment and function of this mast cell population.

【 授权许可】

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