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

TY - JOUR

T1 - Basophil recruitment and IL-4 production during human allergen-induced late asthma

AU - Nouri-Aria, K T

AU - Irani, A M

AU - Jacobson, M R

AU - O'brien, F

AU - Varga, E M

AU - Till, S J

AU - Durham, S R

AU - Schwartz, L B

PY - 2001/8

Y1 - 2001/8

N2 - 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/mm2 at baseline to 8.8 cells/mm2 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.

AB - 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/mm2 at baseline to 8.8 cells/mm2 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.

KW - Respiratory Mucosa

KW - Humans

KW - Asthma

KW - Chemotaxis, Leukocyte

KW - RNA, Messenger

KW - Basophils

KW - In Situ Hybridization

KW - Bronchi

KW - Adult

KW - Interleukin-4

KW - Hypersensitivity, Immediate

KW - Immunohistochemistry

KW - Female

KW - Male

U2 - 10.1067/mai.2001.117175

DO - 10.1067/mai.2001.117175

M3 - Article

C2 - 11496235

SN - 0091-6749

VL - 108

SP - 205

EP - 211

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

M1 - N/A

ER -