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

Abstract

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.

• Authors: Katelijne O De Swert, Kurt G Tournoy, Guy F Joos, Romain A Pauwels
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 113 Issue 6 Pg. 1093-9 (Jun 2004) ISSN: 0091-6749 [Print] United States
• PMID: 15208590 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Neurokinin-1
• Substance P
• Immunoglobulin E
• Ovalbumin

Topics

• Animals
• Asthma (pathology, physiopathology)
• Bronchoalveolar Lavage Fluid (cytology)
• Disease Models, Animal
• Eosinophilia (pathology)
• Immunoglobulin E (blood)
• Lung (pathology, physiopathology)
• Mice
• Mice, Knockout
• Ovalbumin (immunology)
• Receptors, Neurokinin-1 (physiology)
• Substance P (analysis)