Peptide-Containing Nerve Fibers in Human Airways: Distribution and Coexistence Pattern

Luts, A.; Uddman, R.; Alm, Per; Basterra, J; Sundler, F.

doi:10.1159/000236498

Cited by 103 publications

(49 citation statements)

References 40 publications

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“…Substance P is present in nerve profiles, found beneath and within the epithelium and around submucosal glands. 41,42 Furthermore, Chu et al 43 demonstrated that epithelial cells are an additional source of substance P. They also demonstrated expression of the tachykinin NK 1 receptor on goblet cells. Further evidence for this hypothesis is provided by their work demonstrating increased expression of substance P and its receptor in asthmatics, which was correlated with the mucus content in the airway epithelium.…”

Section: Discussionmentioning

confidence: 99%

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

Swert

Tournoy

Joos

et al. 2004

Journal of Allergy and Clinical Immunology

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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

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Section: Discussionmentioning

confidence: 99%

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

Swert

Tournoy

Joos

et al. 2004

Journal of Allergy and Clinical Immunology

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“…In the human airways, they are contained within sensory unmyelinated C nerve fibres, which are distributed beneath or within the airway epithelium, around blood vessels and glands, within the bronchial smooth muscle layer and around local ganglion cells [4][5][6][7][8]. Recent findings in both experimental animals and humans, however, suggest that non-neural cells (endothelial cells, eosinophils and macrophages), either resident or circulating, can also be a source of tachykinins and that immune stimuli can boost tachykinin production from immunocytes [9].…”

mentioning

confidence: 99%

The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics

Schoor¹,

Joos²,

Chasson³

et al. 1998

Eur Respir J

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Substance P (SP) and neurokinin (NK) A are members of the tachykinin peptide family and have been implicated as neurotransmitters which mediate the excitatory part of the nonadrenergic, noncholinergic (e-NANC) nervous system [1][2][3]. In the human airways, they are contained within sensory unmyelinated C nerve fibres, which are distributed beneath or within the airway epithelium, around blood vessels and glands, within the bronchial smooth muscle layer and around local ganglion cells [4][5][6][7][8]. Recent findings in both experimental animals and humans, however, suggest that non-neural cells (endothelial cells, eosinophils and macrophages), either resident or circulating, can also be a source of tachykinins and that immune stimuli can boost tachykinin production from immunocytes [9]. A reduced SP-like immunoreactivity (SP-LI) content of asthmatic airways compared with nonasthmatic subjects has been reported, suggesting an augmented SP release in asthma [10]. Supporting this hypothesis, bronchoalveolar lavage fluid [11] and induced sputum [12] from asthmatics were found to contain increased amounts of SP-LI. SP and NKA contract human airways in vitro and in vivo, NKA being more potent than SP and asthmatics being more sensitive than normal subjects [5,[13][14][15][16][17]. Other potentially important airway effects of tachykinins include mucus secretion, cough, vasodilatation, increased vascular permeability and a broad array of pro-inflammatory effects involving various types of leukocytes [1][2][3].SP and NKA interact with their target cells in the airways through specific tachykinin receptors, with SP being the preferential agonist for the tachykinin NK1 receptor and NKA the preferential agonist for the tachykinin NK2 receptor [18]. Increased expression of NK1 [19] and NK2 [20] tachykinin receptor gene messenger ribonucleic acid (mRNA) in asthmatic airways has been reported. In isolated normal human airways in vitro, tachykinin-induced bronchoconstriction is mediated predominantly by tachykinin NK2 receptors [8,[21][22][23]; recently, however, involvement of tachykinin NK1 receptors has also been noted [24,25]. Tachykinin NK1 receptor stimulation appears to be important in eliciting neurogenic inflammation [1][2][3]18]. On the screening day and during the study periods, increasing concentrations of NKA (3.3×10 -9 to 1.0×10 -6 mol·mL -1 ) were inhaled, until the forced expiratory volume in one second (FEV1) and specific airway conductance (sGaw) decreased by at least 20 and 50%, respectively. During the study periods, 100 mg SR 48968 or matched placebo was ingested in a double-blind, randomized, crossover fashion and NKA provocation was performed at 1.5 and 24 h after dosing. At 1.5 h, the mean (SEM) log10 provocative concentration of NKA causing a 20% fall in FEV1 (PC20 FEV1) was -6.25 (0.20) after SR 48968 and -6.75 (0.17) after placebo (p=0.05); the mean log10 provocative concentration of NKA causing a 35% fall in sGaw (PC35 sGaw) was -7.02 (0.28) after SR 48968 and -7.64 (0.19) after placebo (p=0.05). A...

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“…Nerve fibres containing vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) are seen around pulmonary blood vessels and close to small bronchioles [3]. Endocrine cells, solitary as well as clustered, can be seen in bronchi and bronchioles [4].…”

mentioning

confidence: 99%

Low plasma concentrations of VIP and elevated levels of other neuropeptides during exacerbations of asthma

Cardell¹,

Uddman²,

Edvinsson³

1994

Eur Respir J

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Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory cells. Their widespread distribution and physiological effects suggest that they may play important roles in asthma. We investigated whether, during an exacerbation of asthma, patients displayed changes in plasma levels of the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25 adult patients attending the emergency ward with an exacerbation of asthma was sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY-like immunoreactivity (-LI) were determined by immunoassay, and the results obtained were compared with findings in 21 healthy controls. The mean plasma levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1), SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1, respectively). A relationship was seen between the reversibility of obstruction, expressed as improvement of peak expiratory flow upon treatment, and the neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and CGRP-LI in particular, may therefore be employed as predictors of responsiveness to bronchodilatory therapy.

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Peptide-Containing Nerve Fibers in Human Airways: Distribution and Coexistence Pattern

Cited by 103 publications

References 40 publications

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

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

The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics

Low plasma concentrations of VIP and elevated levels of other neuropeptides during exacerbations of asthma

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