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

Authors

Yogesh Saini, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.
Brandon W. Lewis, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.
Dongfang Yu, Marsico Lung Institute/Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Hong Dang, Marsico Lung Institute/Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Alessandra Livraghi-Butrico, Marsico Lung Institute/Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Fabio Del Piero, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.
Wanda K. O'Neal, Marsico Lung Institute/Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Richard C. Boucher, Marsico Lung Institute/Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Document Type

Article

Publication Date

4-1-2018

Abstract

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 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) MΦ, and the recovered MΦ were immature, phenotypically distinct, and functionally defective. DTA+/Scnn1b-Tg mice exhibited a similar depletion of LysM+ MΦ offset by a significant increase in LysM- MΦ 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-α, 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 MΦ in stressed airspaces is responded via compensatory increase in the recruitment of immature MΦ and altered non-MΦ effector cell-centered responses, for example, mucus production and adaptive immune defense. Overall, these data identify dynamic roles of MΦ in moderating, rather than exacerbating, the severity of lung disease in a model of CB.

Publication Source (Journal or Book title)

Physiological reports

First Page

e13677

Recommended Citation

Saini, Y., Lewis, B. W., Yu, D., Dang, H., Livraghi-Butrico, A., Del Piero, F., O'Neal, W. K., & Boucher, R. C. (2018). Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis. Physiological reports, 6 (8), e13677. https://doi.org/10.14814/phy2.13677