BACKGROUND: Tachykinins are present in sensory nerves and in nonneuronal cells like macrophages. Human data suggest a role for these peptides in asthma, but the exact role of tachykinins and their receptors in allergic airway inflammation is still a matter of debate. OBJECTIVE: The aim of this study was to determine the role of the tachykinin NK1 receptor in allergic airway responses in a mouse model. METHODS: Tachykinin NK1 receptor wild-type and knockout animals were sensitized intraperitoneally to ovalbumin and subsequently exposed from days 14 to 21 to aerosolized ovalbumin (1% ). On day 22, the immunologic and histologic changes were evaluated, and lung function measurements were performed. RESULTS: Mice lacking the tachykinin NK1 receptor and their wild-type litter mates developed inflammatory cell infiltrates in the airways and ovalbumin-specific IgE on sensitization and exposure to ovalbumin compared with saline-exposed controls. No differences were detected between wild-type and knockout mice. The substance P content of alveolar macrophages was not influenced by ovalbumin or by the lack of the NK1 receptor. Ovalbumin-induced hyperresponsiveness was not observed, but at baseline, the knockout mice were more reactive despite similar morphology. Ovalbumin induced more goblet cell hyperplasia in wild-type animals compared with knockout animals. No differences in airway wall thickness were observed. CONCLUSION: These data suggest that tachykinin NK1 receptors do not affect allergic airway inflammation or endogenous substance P content of alveolar macrophages but influence baseline responsiveness and promote features of remodeling such as goblet cell hyperplasia.
BACKGROUND: Tachykinins are present in sensory nerves and in nonneuronal cells like macrophages. Human data suggest a role for these peptides in asthma, but the exact role of tachykinins and their receptors in allergic airway inflammation is still a matter of debate. OBJECTIVE: The aim of this study was to determine the role of the tachykinin NK1 receptor in allergic airway responses in a mouse model. METHODS: Tachykinin NK1 receptor wild-type and knockout animals were sensitized intraperitoneally to ovalbumin and subsequently exposed from days 14 to 21 to aerosolized ovalbumin (1% ). On day 22, the immunologic and histologic changes were evaluated, and lung function measurements were performed. RESULTS:Mice lacking the tachykinin NK1 receptor and their wild-type litter mates developed inflammatory cell infiltrates in the airways and ovalbumin-specific IgE on sensitization and exposure to ovalbumin compared with saline-exposed controls. No differences were detected between wild-type and knockout mice. The substance P content of alveolar macrophages was not influenced by ovalbumin or by the lack of the NK1 receptor. Ovalbumin-induced hyperresponsiveness was not observed, but at baseline, the knockout mice were more reactive despite similar morphology. Ovalbumin induced more goblet cell hyperplasia in wild-type animals compared with knockout animals. No differences in airway wall thickness were observed. CONCLUSION: These data suggest that tachykinin NK1 receptors do not affect allergic airway inflammation or endogenous substance P content of alveolar macrophages but influence baseline responsiveness and promote features of remodeling such as goblet cell hyperplasia.