title: Basophil recruitment and IL-4 production during human allergen-induced late asthma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Upper Respiratory Medicine, Imperial College at National Heart & Lung Institute and Royal Brompton Hospital, London, United Kingdom.
authors.forename: K T
authors.initials: KT
authors.lastname: Nouri-Aria
authors.forename: A M
authors.initials: AM
authors.lastname: Irani
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: F
authors.initials: F
authors.lastname: O'brien
authors.forename: E M
authors.initials: EM
authors.lastname: Varga
authors.forename: S J
authors.initials: SJ
authors.lastname: Till
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: L B
authors.initials: LB
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000302:isolation & purification; D020545:Respiratory Mucosa / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4