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Am. J. Respir. Crit. Care Med., Volume 158, Number 1, July 1998, 233-240

Increased Expression of High Affinity IgE (Fcepsilon RI) Receptor-alpha Chain mRNA and Protein-bearing Eosinophils in Human Allergen-induced Atopic Asthma

KARALASINGAM RAJAKULASINGAM, STEPHEN TILL, SUN YING, MARC HUMBERT, JULIA BARKANS, MARK SULLIVAN, QIU MENG, CHRISTOPHER J. CORRIGAN, JATINDER BUNGRE, J. ANDREW GRANT, A. BARRY KAY, and STEPHEN R. DURHAM

Upper Respiratory Medicine and Allergy and Clinical Immunology, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London, United Kingdom; Allergy and Immunology Division, Department of Medicine, University of Texas Medical Branch, Galveston, Texas

Fcvarepsilon 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 Fcvarepsilon RI by tissue eosinophils in atopic asthma after allergen challenge has not been established. For this reason we attempted to identify mRNA and protein product + Fcvarepsilon RIalpha 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 Fcvarepsilon RIalpha was determined using in situ hybridization and Fcvarepsilon RIalpha protein expression by immunocytochemistry using a mouse monoclonal antibody 22E7. Colocalization of Fcvarepsilon RIalpha receptors to eosinophils was performed using chromotrope 2R. When compared with a control challenge, segmental challenge with Dermatophagoides pteronyssinus induced significant BAL eosinophilia (p = 0.007). The total number of BAL Fcvarepsilon RIalpha mRNA and protein-positive cells also increased in asthmatics, median values 2 (0.7-7.2) and 11.5 (0.6-65.0) × 106 cells (p = 0.02) and 0 (0-0.3 × 106) and 3.1 × 106 (0.45 - 162.5 × 106) cells (p = 0.007), respectively, for mRNA and protein. Net increases in Fcvarepsilon RIalpha + 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 Fcvarepsilon RIalpha + cells were eosinophils after control challenge and, in contrast, 85 to 95% of Fcvarepsilon RIalpha + cells were eosinophils after allergen. There were no differences in the numbers of Fcvarepsilon RIalpha + 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 Fcvarepsilon RIalpha predominantly on BAL eosinophils.




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