Basophil recruitment and IL-4 production during human allergen-induced late asthma

Background: Basophils represent an important source of inflammatory mediato rs 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 expre ss IL-4 mRNA and protein during allergen-induced late asthmatic responses. Methods: Fiberoptic bronchoscopic bronchial biopsies were obtained at 24 ho urs from sites of segmental bronchial allergen challenge and control sites in 19 patients with atopic asthma and 6 nonatopic healthy volunteers. Basop hil numbers were assessed by immunohistochemistry through use of mAb 2D7. I L-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 basoph ils through use of dual immunohistochemistry. Results: After allergen challenge, there was an increase in the median numb er 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) aft er challenge; P=.002), which also was significantly higher than what was se en in nonasthmatic controls (P=.01). Similarly, IL-4 mRNA-positive cells we re 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-chal lenge expressed, respectively, IL-4 mRNA and protein. Conversely, 19% of IL -4 mRNA-positive cells and 72% of IL-4 protein-positive cells were accounte d for by basophils. Conclusion: After allergen provocation in sensitive patients with atopic as thma, basophils are recruited to the bronchial mucosa and express IL-4 mRNA and protein, which might contribute to local IgE synthesis and/or tissue e osinophilia or other aspects of allergic inflammation during late responses and ongoing asthma.