Neutrophils recruited to the lungs of humans by segmental antigen challenge display a reduced chemotactic response to leukotriene B4.
Allergic asthma is characterized by an infiltration of the lung with inflammatory cells including eosinophils and neutrophils. The mechanism by which inflammatory cells are recruited to the lung in IgE-mediated disorders is unknown. In order to explore the mechanism responsible for cell recruitment, ragweed-allergic volunteers underwent segmental (bronchoscopic) antigen challenge, followed 24 h later by bronchoalveolar lavage (BAL). Experimental conditions were chosen to favor neutrophil, rather than eosinophil, recruitment. Chemotactic responses of purified BAL neutrophils (under agarose) were then compared with blood neutrophils obtained from the same subjects. We hypothesized that neutrophils recruited to the lung would be desensitized to the chemotaxin(s) responsible for their recruitment. BAL neutrophils showed a profound inhibition of their chemotactic response to an optimal concentration of leukotriene B4 (LTB4) ex vivo (approximately 40% of the response of blood neutrophils) with a slightly reduced response to the anaphylatoxin C5a and to FMLP. In addition, they displayed a normal production of superoxide anion in response to phorbol myristate acetate. These results demonstrate that neutrophils recruited to the lung of humans by local antigen challenge display a marked inhibition of their chemotactic response to LTB4, and are consistent with the hypothesis that LTB4 is instrumental in recruiting neutrophils to the lung in IgE-mediated reactions.
Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, 19107-5083.
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Koh
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Dupuis
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Pollice
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Albertine
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Fish
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Peters
D000328:Adult; D000485:Allergens / Q000276:immunology; D000486:Allergy and Immunology; D052179:Antigens, Plant; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D010940:Plant Proteins; D015203:Reproducibility of Results
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D010940:Plant Proteins; D007975:Leukotriene B4