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  • Title: Basophil recruitment and IL-4 production during human allergen-induced late asthma.
    Author: Nouri-Aria KT, Irani AM, Jacobson MR, O'brien F, Varga EM, Till SJ, Durham SR, Schwartz LB.
    Journal: J Allergy Clin Immunol; 2001 Aug; 108(2):205-11. PubMed ID: 11496235.
    Abstract:
    BACKGROUND: Basophils represent an important source of inflammatory mediators and cytokines after IgE-dependent activation in human beings. OBJECTIVE: To assess the role of basophils in allergic asthma, we measured the number of basophils in the bronchial mucosa and their capacity to express IL-4 mRNA and protein during allergen-induced late asthmatic responses. METHODS: Fiberoptic bronchoscopic bronchial biopsies were obtained at 24 hours from sites of segmental bronchial allergen challenge and control sites in 19 patients with atopic asthma and 6 nonatopic healthy volunteers. Basophil numbers were assessed by immunohistochemistry through use of mAb 2D7. IL-4 mRNA--positive cells were detected through use of in situ hybridization and colocalized to basophils through use of sequential immunohistochemistry/in situ hybridization. IL-4 protein was detected and colocalized to basophils through use of dual immunohistochemistry. RESULTS: After allergen challenge, there was an increase in the median number of 2D7-positive basophils per square millimeter in the bronchial mucosa in patients with asthma (0.9 cells/mm(2) at baseline to 8.8 cells/mm(2) after challenge; P =.002), which also was significantly higher than what was seen in nonasthmatic controls (P =.01). Similarly, IL-4 mRNA--positive cells were increased at 24 hours in patients with asthma (1.4 to 14) in comparison with controls (0 to 0; P =.02). Colocalization studies revealed that 15% and 41% of the basophil population in patients with asthma after allergen-challenge expressed, respectively, IL-4 mRNA and protein. Conversely, 19% of IL-4 mRNA-positive cells and 72% of IL-4 protein--positive cells were accounted for by basophils. CONCLUSION: After allergen provocation in sensitive patients with atopic asthma, basophils are recruited to the bronchial mucosa and express IL-4 mRNA and protein, which might contribute to local IgE synthesis and/or tissue eosinophilia or other aspects of allergic inflammation during late responses and ongoing asthma.
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