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 NK 1 receptor in allergic airway responses in a mouse model. Methods: Tachykinin NK 1 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 NK 1 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 NK 1 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 NK 1 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

Neurokinin‐1 receptor activation induces reactive oxygen species and epithelial damage in allergic airway inflammation

“…Our results demonstrate that SPinduced ROS generation is involved in the damage and the remodelling of the bronchial epithelium in vivo, as a strong reduction of both the damage and the goblet cell hyperplasia was observed after treating the animals with SR 140333 or NAC, respectively. While an earlier study did not find a reduction of epithelial damage in NK1 knockout mice, the promotion of remodelling was shown to be related to the NK-1 receptor, as seen in goblet cell hyperplasia [40], which was also seen in our model, but the earlier study did not assess the role of ROS in this context. NK-1 inhibition resulted in decreased inflammatory cell influx to airway tissues and BAL fluid, which has also been observed in an earlier study [41].…”

Lack of Transient Receptor Potential Vanilloid-1 Enhances Th2-Biased Immune Response of the Airways in Mice Receiving Intranasal, but Not Intraperitoneal, Sensitization

“…When given i.p. sensitization, several investigators found that there was no difference in BHR between animals with and without sensitization [19,29,30,31], while others indicated an increased bronchial responsiveness in animals given OVA compared to vehicle [28,32,33]. As for animals sensitized with i.n.…”

Role of the tachykinin NK1 receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea

“…The observed contractile response to antigen is due to activation of mast cells via antigen cross-linking of IgE antibodies bound on the high affinity IgE receptor FcεRI [24]. It is important to note that no differences in serum ovalbumin-specific IgE levels between the tachykinin NK 1 receptor WT and KO mice can be detected [25]. Upon activation, mast cells previously been demonstrated in rats [17] and in mice but this depended on the inbred strain of mice used [16;18].…”