Neuroimmune dysregulation in a mouse model for allergic asthma

Abstract

Rationale Dysregulated neuroimmuno pathways are thought to play an important role in the pathogenesis of allergic asthma. Recent data indicate that neurotrophins and the corresponding receptors contribute to the regulation of airway inflammation, broncho-construction and airway hyperresponsiveness. In the present study we investigated the contribution of neurotrophins and their receptors in a mouse model for allergic asthma and focused on the role of the pan-neurotrophin receptor p75. Methods To classify the role of p75 we established a mouse model for allergic asthma. The expression of the pan-neurotrophin receptor was examined by immunohistochemistry of the lung. In addition, the contribution of p75 to airway inflammation and airway hyperresponsiveness was defined in p75-/- mice as well as in wildtype mice treated with an inhibitory anti-p75 antibody. Results The pan-neurotrophin receptor p75 is expressed both in normal and asthmatic lungs and airways. Additional p75 immunoreactivity was found within the inflammatory infiltrates of OVA sensitized and challenged mice. The analysis of p75-/- mice and mice treated with the anti-p75 antibody indicated uniformly that the influx of eosinophils is to a large extent dependent upon functional p75 receptor expression. Furthermore, airway hyperresponsiveness to capsaicin but not to methacholine depends entirely on this receptor. Conclusions Our data indicate that p75 plays an important role in allergic asthma. Airway inflammation and hyperresponsiveness to capsaicin depend to a large extend on the pan-neurotrophin receptor p75. The involvement of the specific neurotrophin receptors, TrkA, TrkB and TrkC, remains to be elucidated.