Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats

Autor: I-Hsuan Huang, Nai-Ju Chan, Yueh-Yin Chen, You Shuei Lin, Sheng-Hsuan Lan, Chun-Chun Hsu, Chia Ling Chen
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
beta-Glucans
sensory neuron
afferent sensitization
Pharmacology
lcsh:Chemistry
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Receptor
lcsh:QH301-705.5
Glucans
Lung
TRPA1 Cation Channel
Spectroscopy
Sensitization
Cells
Cultured
Respiration
Vagus Nerve
General Medicine
glucan
respiratory system
Computer Science Applications
medicine.anatomical_structure
airway hypersensitivity
Dectin-1
Sensory Receptor Cells
TRPV1
TRPA1
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Reflex
medicine
Respiratory Hypersensitivity
Animals
Lectins
C-Type
Neurons
Afferent
Physical and Theoretical Chemistry
Molecular Biology
business.industry
Organic Chemistry
capsaicin-sensitive lung vagal afferents
Sensory neuron
respiratory tract diseases
Acetylcysteine
Rats
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
030228 respiratory system
chemistry
Capsaicin
Purines
Acetanilides
fungi
Airway
business
Reactive Oxygen Species
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 6845, p 6845 (2020)
Volume 21
Issue 18
ISSN: 1422-0067
Popis: Airway exposure to 1,3-&beta
D-glucan (&beta
glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated
however, the mechanism underlying &beta
glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs. Activation of CSLV afferents triggers several airway reflexes, such as cough. Furthermore, the sensitization of these afferents is known to contribute to the airway hypersensitivity during pulmonary inflammation. This study was carried out to determine whether &beta
glucan induces airway hypersensitivity and the role of the CSLV neurons in this hypersensitivity. Our results showed that the intratracheal instillation of &beta
glucan caused not only a distinctly irregular pattern in baseline breathing, but also induced a marked enhancement in the pulmonary chemoreflex responses to capsaicin in anesthetized, spontaneously breathing rats. The potentiating effect of &beta
glucan was found 45 min later and persisted at 90 min. However, &beta
glucan no longer caused the irregular baseline breathing and the potentiating of pulmonary chemoreflex responses after treatment with perineural capsaicin treatment that blocked the conduction of CSLV fibers. Besides, the potentiating effect of &beta
glucan on pulmonary chemoreflex responses was significantly attenuated by N-acetyl-L-cysteine (a ROS scavenger), HC-030031 (a TRPA1 antagonist), and Laminarin (a Dectin-1 antagonist). A combination of Laminarin and HC-030031 further reduced the &beta
glucan-induced effect. Indeed, our fiber activity results showed that the baseline fiber activity and the sensitivity of CSLV afferents were markedly elevated by &beta
glucan instillation, with a similar timeframe in anesthetized, artificially ventilated rats. Moreover, this effect was reduced by treatment with HC-030031. In isolated rat CSLV neurons, the &beta
glucan perfusion caused a similar pattern of potentiating effects on capsaicin-induced Ca2+ transients, and &beta
glucan-induced sensitization was abolished by Laminarin pretreatment. Furthermore, the immunofluorescence results showed that there was a co-localization of TRPV1 and Dectin-1 expression in the DiI-labeled lung vagal neurons. These results suggest that CSLV afferents play a vital role in the airway hypersensitivity elicited by airway exposure to &beta
glucan. The TRPA1 and Dectin-1 receptors appear to be primarily responsible for generating &beta
glucan-induced airway hypersensitivity.
Databáze: OpenAIRE
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