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Eosinophils increase airway sensory nerve density in mice and in human asthma.

ABSTRACT: In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airway innervation and substance P expression were increased in moderate persistent asthmatics compared to mild intermittent asthmatics and healthy subjects. Increased innervation was associated with a lack of bronchodilator responsiveness and increased irritant sensitivity. In a mouse model of eosinophilic airway inflammation, the increase in nerve density and airway hyperresponsiveness were mediated by eosinophils. Our results implicate airway nerve remodeling as a key mechanism for increased irritant sensitivity and exaggerated airway responsiveness in eosinophilic asthma.

SUBMITTER: Drake MG

PROVIDER: S-EPMC6592848 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Eosinophils increase airway sensory nerve density in mice and in human asthma.

Drake Matthew G MG Scott Gregory D GD Blum Emily D ED Lebold Katherine M KM Nie Zhenying Z Lee James J JJ Fryer Allison D AD Costello Richard W RW Jacoby David B DB

Science translational medicine 20180901 457

In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airw ...[more]

PMID: 30185653

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Project description:OBJECTIVE:We aimed to investigate peripheral blood eosinophil chemotaxis, generation of spontaneous reactive oxygen species (ROS), and apoptosis in patients with allergic asthma after bronchial allergen challenge. MATERIAL AND METHODS:A total of 18 patients with allergic asthma (AA), 14 with allergic rhinitis (AR), and 10 healthy subjects (HS) underwent bronchial challenge with a specific allergen extract. Eosinophils from peripheral blood were isolated 24 h before as well as 7 and 24 h after bronchial allergen challenge. Chemotaxis, spontaneous ROS production in eosinophils, and apoptosis were analyzed by flow cytometry. Serum and induced sputum IL-5 levels were measured by ELISA; the cell count in sputum was analyzed by the May-Grünwald-Giemsa method. RESULTS:Before bronchial allergen challenge, peripheral blood eosinophil chemotaxis, spontaneous ROS production was enhanced and eosinophil apoptosis was reduced in the patients with AA as compared with AR patients and HS (P?<?0.05). Meanwhile, eosinophil chemotaxis and ROS generation markedly increased in the patients with AA 7 h and 24 h after challenge compared with other groups and baseline values (P?<?0.05). The percentage of apoptotic eosinophils in the patients with AA decreased at 7 h as well as 24 h after challenge when compared with other groups and the baseline values (P?<?0.05). There was a significant correlation between the migrated peripheral blood eosinophil count and the sputum eosinophil count (Rs?=?0.89, P?<?0.0001) and the sputum IL-5 level (Rs?=?0.68, P?=?0.002) at 24 h after bronchial challenge only in the patients with AA. Furthermore, the percentage of peripheral blood apoptotic eosinophils significantly correlated with eosinophil count in sputum (Rs?=?-0.53, P?=?0.02), and ROS production correlated with the serum IL-5 levels (Rs?=?0.71, P?=?0.01). CONCLUSION:During allergen-induced late-phase airway inflammation, peripheral blood eosinophils demonstrated further alterations of their functional activity manifested by enhanced spontaneous ROS production, increased chemotaxis, and diminished apoptosis in patients with AA.

Dataset Information

Eosinophils increase airway sensory nerve density in mice and in human asthma.

Publications

Eosinophils increase airway sensory nerve density in mice and in human asthma.

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