Airway goblet cell hyperplasia in asthma: hypersecretory and anti‐inflammatory?

Rogers, Duncan F.

doi:10.1046/j.1365-2745.2002.01474.x

Cited by 63 publications

(42 citation statements)

References 30 publications

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“…First, inhaled allergens induce a T H 2 lymphocyte response with release of cytokines that induce goblet cell hyperplasia either directly or indirectly. 36 As substance P 37 and its receptor 38,39 are expressed in and on lymphocytes, these cells may be influenced in an autocrine or paracrine fashion to augment the release of these cytokines. Several studies have already shown that substance P is able to modulate the chemotaxis, proliferation, and activation of lymphocytes.…”

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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“…[41][42][43] In addition, tears and transudation from blood vessels add fluid to the nasal secretions. They are a long, thread-like, complex glycoconjugates consisting of a linear peptide backbone (apomucin), which is encoded by specific mucin (MUC) genes.…”

Section: Mucinmentioning

confidence: 99%

The Effect of Cilia and the Mucociliary Clearance on Successful Drug Delivery

Gizurarson

2015

Biological & Pharmaceutical Bulletin

101

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Nasal mucociliary clearance is one of the most important factors affecting nasal delivery of drugs and vaccines. This is also the most important physiological defense mechanism inside the nasal cavity. It removes inhaled (and delivered) particles, microbes and substances trapped in the mucus. Almost all inhaled particles are trapped in the mucus carpet and transported with a rate of 8-10 mm/h toward the pharynx. This transport is conducted by the ciliated cells, which contain about 100-250 motile cellular appendages called cilia, 0.3 µm wide and 5 µm in length that beat about 1000 times every minute or 12-15 Hz. For efficient mucociliary clearance, the interaction between the cilia and the nasal mucus needs to be well structured, where the mucus layer is a tri-layer: an upper gel layer that floats on the lower, more aqueous solution, called the periciliary liquid layer and a third layer of surfactants between these two main layers. Pharmacokinetic calculations of the mucociliary clearance show that this mechanism may account for a substantial difference in bioavailability following nasal delivery. If the formulation irritates the nasal mucosa, this mechanism will cause the irritant to be rapidly diluted, followed by increased clearance, and swallowed. The result is a much shorter duration inside the nasal cavity and therefore less nasal bioavailability.

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“…Goblet cells, which are known to produce mucus and are absent in small airways of normal individuals (Jeffery and Zhu, 2002), are observed in chronic airway inflammatory conditions and contribute to bronchiolar obstruction (Rogers, 2002). Thus, the observed reduction in mucus production in kefir-treated lung tissue may be attributed to the substantial drop in Th2 cytokine levels, as well as the reduction in eosinophilia in asthmatic mice.…”

Section: Article In Pressmentioning

confidence: 99%