Increased expression of high affinity IgE (FcεRI) receptor-α chain mRNA and protein-bearing eosinophils in human allergen-induced atopic asthma

被引:47
作者
Rajakulasingam, K
Till, S
Ying, S
Humbert, M
Barkans, J
Sullivan, M
Meng, Q
Corrigan, CJ
Bungre, J
Grant, JA
Kay, AB
Durham, SR
机构
[1] Natl Heart & Lung Inst, Imperial Coll, Sch Med, London, England
[2] Univ Texas, Med Branch, Dept Med, Allergy & Immunol Div, Galveston, TX 77550 USA
关键词
D O I
10.1164/ajrccm.158.1.9708106
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Fc epsilon RI receptors play an important role in allergen-induced mediator release and antigen presentation by mast cells, basophils, and monocyte/macrophages in atopic disorders. The expression of Fc epsilon RI by tissue eosinophils in atopic asthma after allergen challenge has not been established. Far this reason we attempted to identify mRNA and protein product + Fc epsilon RI alpha eosinophils in cytospins made from bronchoalveolar lavage (BAL) from atopic asthmatics (n = 9) and nonatopic normal subjects (n = 4) 24 h after segmental challenge with allergen or diluent. Messenger RNA for Fc epsilon RI alpha was determined using in situ hybridization and Fc epsilon RI alpha protein expression by immunocytochemistry using a mouse monoclonal antibody 22E7. Colocalization of FceRIa receptors to eosinophils was performed using chromotrope 2R. When compared with a control challenge, segmental challenge with Dermotophagoides pteronyssinus induced significant BAL eosinophilia (p = 0.007). The total number of BAL Fc epsilon RI alpha mRNA and protein-positive cells also increased in asthmatics, median values 2 (0.7-7.2) and 11.5 (0.6-65.0) x 10(6) cells (p = 0.02) and 0 (0-0.3 x 10(6)) and 3.1 x 10(6) (0.45 - 162.5 x 10(6)) cells (p = 0.007), respectively, for mRNA and protein. Net increases in Fc epsilon RI alpha+ cells correlated with the net increases in BAL eosinophils (r = 0.98, p = 0.0001 for mRNA and r = 0.72 p = 0.02 for protein). Colocalization studies with chromotrope 2R revealed that only 4% of Fc epsilon RI alpha+ cells were eosinophils after control challenge and, in contrast, 85 to 95% of Fc epsilon RI alpha+ cells were eosinophils after allergen. There were no differences in the numbers of Fc epsilon RI alpha+ cells or eosinophils in normal control subjects. Our results demonstrated that local endobronchial allergen provocation in atopic asthmatics results in increased synthesis and expression of Fc epsilon RI alpha predominantly on BAL eosinophils.
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页码:233 / 240
页数:8
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