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Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program.

Abstract：

RATIONALE:Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. OBJECTIVES:To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance. METHODS:Endobronchial biopsies, epithelial brushings, and bronchoalveolar lavage were obtained from subjects with asthma and normal subjects from the Severe Asthma Research Program (N = 199). Tryptase, chymase, and carboxypeptidase A (CPA)3 were used to identify total MC (MC(Tot)) and the MC(TC) subset (MCs positive for both tryptase and chymase) using immunostaining and quantitative real-time polymerase chain reaction. Lavage was analyzed for tryptase and prostaglandin D2 (PGD2) by ELISA. MEASUREMENTS AND MAIN RESULTS:Submucosal MC(Tot) (tryptase-positive by immunostaining) numbers were highest in "mild asthma/no inhaled corticosteroid (ICS) therapy" subjects and decreased with greater asthma severity (P = 0.002). In contrast, MC(TC) (chymase-positive by immunostaining) were the predominant (MC(TC)/MC(Tot) > 50%) MC phenotype in SA (overall P = 0.005). Epithelial MC(Tot) were also highest in mild asthma/no ICS, but were not lower in SA. Instead, they persisted and were predominantly MC(TC). Epithelial CPA3 and tryptase mRNA supported the immunostaining data (overall P = 0.008 and P = 0.02, respectively). Lavage PGD2 was higher in SA than in other steroid-treated groups (overall P = 0.02), whereas tryptase did not differentiate the groups. In statistical models, PGD2 and MC(TC)/MC(Tot) predicted SA. CONCLUSIONS:Severe asthma is associated with a predominance of MC(TC) in the airway submucosa and epithelium. Activation of those MC(TC) may contribute to the increases in PGD2 levels. The data suggest an altered and active MC population contributes to SA pathology.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Balzar S,Fajt ML,Comhair SA,Erzurum SC,Bleecker E,Busse WW,Castro M,Gaston B,Israel E,Schwartz LB,Curran-Everett D,Moore CG,Wenzel SE

doi

10.1164/rccm.201002-0295OC

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

299-309

issue

eissn

1073-449X

issn

1535-4970

pii

201002-0295OC

journal_volume

183

pub_type

杂志文章

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Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program.