Airway Exposure to 1,3-Beta-d-Glucan Induces Airway Hyperresponsiveness in Guinea Pigs

ACS Pharmacology & Translational Science(2022)

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摘要
1,3-Beta-D-glucan (beta-glucan) is a component of mold cell walls and is frequently found in fungi and house dust mites. The studies of beta-glucan are inconsistent, although it has been implicated in airway adverse responses. This study was carried out to determine whether airway hyperresponsiveness was seen 24 h after airway exposure to beta-glucan in guinea pigs. Two matching guinea pigs were exposed intratracheally to either beta-glucan or its vehicle. Twenty-four hours after intratracheal instillation, there was no difference between these two groups in the baseline of the total pulmonary resistance (R-L), dynamic lung compliance (C-dyn), arterial blood pressure, and heart rate. In contrast, the responses of R-L to capsaicin injection were significantly increased in beta-glucan animals; capsaicin at the same dose of 3.2 mu g/kg increased R-L by 184% in vehicle animals and by 400% in beta-glucan animals. The effective dose 200% to capsaicin injection was lower in the beta-glucan animals. Furthermore, the increases in R-L were partially reduced after transient lung hyperinflation to recruit the occluding airways; however, the R-L induced by capsaicin injection after lung hyperinflation was significantly larger than the baseline in beta-glucan animals; also, the lung wet-to-dry ratio in capsaicin-injected animals was augmented in the beta-glucan group. Moreover, the airway hyperresponsiveness was accompanied by increases in neutrophils in the bronchoalveolar lavage fluid in the beta-glucan animals. Furthermore, the levels of substance P and the calcitonin gene-related peptide in the bronchoalveolar lavage fluid collected after capsaicin injection were increased in beta-glucan animals. We provide definitive evidence that beta-glucan can induce airway hyperresponsiveness in guinea pigs, and the neuropeptide releases play an important role in this airway hyperresponsiveness.
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关键词
airway hyperresponsiveness,airway in fl ammation,bronchoconstriction,capsaicin,glucan
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