The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma.
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.


CONCLUSIONS
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.
De Swert
Katelijne O
KO
Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Katelijne.Deswert@UGent.be
Tournoy
Kurt G
KG
Joos
Guy F
GF
Pauwels
Romain A
RA
D000818:Animals; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000032:analysis
D018040:Receptors, Neurokinin-1; D013373:Substance P; D007073:Immunoglobulin E; D010047:Ovalbumin