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Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

ABSTRACT: Macrophages (M?) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, M? are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers M? to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial M?-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age. Compared with DTA- littermates, the DTA+ mice had ~50% reduction in bronchoalveolar lavage (BAL) M?, and the recovered M? were immature, phenotypically distinct, and functionally defective. DTA+/Scnn1b-Tg mice exhibited a similar depletion of LysM+ M? offset by a significant increase in LysM- M? in the BAL. In DTA+/Scnn1b-Tg mice, lung disease was more severe than in DTA-/Scnn1b-Tg littermates, as indicated by an increased incidence of mucus plugging, mucous cells, airway inflammation, higher levels of cytokines/chemokines (KC, TNF-?, MIP-2, M-CSF, IL-5, and IL-17), and worsened alveolar airspace enlargement. DTA+/Scnn1b-Tg mice exhibited increased occurrence of lymphoid nodules, which was concomitant with elevated levels of immunoglobulins in BAL. Collectively, these data indicate that numerical deficiency of M? in stressed airspaces is responded via compensatory increase in the recruitment of immature M? and altered non-M? effector cell-centered responses, for example, mucus production and adaptive immune defense. Overall, these data identify dynamic roles of M? in moderating, rather than exacerbating, the severity of lung disease in a model of CB.

SUBMITTER: Saini Y

PROVIDER: S-EPMC5904692 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

Saini Yogesh Y Lewis Brandon W BW Yu Dongfang D Dang Hong H Livraghi-Butrico Alessandra A Del Piero Fabio F O'Neal Wanda K WK Boucher Richard C RC

Physiological reports 20180401 8

Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crosse ...[more]

PMID: 29667749

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Project description:BackgroundChronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores.MethodsThis study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB.ResultsAmong the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB.ConclusionsCB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Dataset Information

Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

Publications

Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

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