Atropine‐induced potentiation of airway hyperreactivity in antigen challenged guinea pigs is mediated by nerve growth factor

Abstract

Eosinophils accumulate around airway nerves and cause airway hyperreactivity in antigen challenged guinea pigs. Anticholinergic drugs such as atropine reverse airway hyperreactivity in challenged animals. Similarly, anticholinergics reverse asthma exacerbations in man; however, they are less effective in managing chronic asthma. Conversely, atropine administration to sensitized guinea pigs 1h before challenge significantly potentiates airway hyperreactivity measured 24h later and is mediated by eosinophils. Since eosinophils produce nerve growth factor (NGF), we tested whether NGF causes atropine‐potentiated hyperreactivity. Sensitized guinea pigs were given antibody to NGF (AbNGF) 1h before challenge. Electrical stimulation of both vagus nerves caused bronchoconstriction that was potentiated in challenged animals. Atropine pretreatment further potentiated vagally induced bronchoconstriction in challenged animals, an effect blocked by AbNGF. Atropine‐induced increase in eosinophil protein deposition (assessed by immunohistochemistry) in challenged animals was blocked by AbNGF. Thus, NGF mediates atropine‐induced potentiation of airway hyperreactivity, possibly due to increased eosinophil activation. These data suggest that anticholinergics enhance eosinophil interactions with airway nerves via neurotrophins.NIH HL55543 HL54659 ES014601 HL071795 AHA 0515486Z