Increased Monocyte-Derived CD11b+ Macrophage Subpopulations Following Cigarette Smoke Exposure Are Associated With
Steven P Cass1, Olivia Mekhael1, Danya Thayaparan1
1Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada.
Rationale:
The accumulation of macrophages in the airways and the pulmonary interstitium is a hallmark of cigarette smoke-associated inflammation. Notably, pulmonary macrophages are not a homogenous population but consist of several subpopulations. To date, the manner in which cigarette smoke exposure affects the relative composition and functional capacity of macrophage subpopulations has not been elucidated.
Methods:
Using a whole-body cigarette smoke exposure system, we investigated the impact of cigarette smoke on macrophage subpopulations in C57BL/6 mice using flow cytometry-based approaches. Moreover, we used bromodeoxyuridine labelling plus Il1a and Il1r1 mice to assess the relative contribution of local proliferation and monocyte recruitment to macrophage accumulation. To assess the functional consequences of altered macrophage subpopulations, we used a model of concurrent bleomycin-induced lung injury and cigarette smoke exposure to examine tissue remodelling processes.
Main Results:
Cigarette smoke exposure altered the composition of pulmonary macrophages increasing CD11b+ subpopulations including monocyte-derived alveolar macrophages (Mo-AM) as well as interstitial macrophages (IM)1, -2 and -3. The increase in CD11b+ subpopulations was observed at multiple cigarette smoke exposure timepoints. Bromodeoxyuridine labelling and studies in Il1a mice demonstrated that increased Mo-AM and IM3 turnover in the lungs of cigarette smoke-exposed mice was IL-1α dependent. Compositional changes in macrophage subpopulations were associated with impaired induction of fibrogenesis including decreased α-smooth muscle actin positive cells following intratracheal bleomycin treatment. Mechanistically, in vivo and ex vivo assays demonstrated predominant macrophage M1 polarisation and reduced matrix metallopeptidase 9 activity in cigarette smoke-exposed mice.
Conclusion:
Cigarette smoke exposure modified the composition of pulmonary macrophage by expanding CD11b+ subpopulations. These compositional changes were associated with attenuated fibrogenesis, as well as predominant M1 polarisation and decreased fibrotic activity. Overall, these data suggest that cigarette smoke exposure altered the composition of pulmonary macrophage subpopulations contributing to impaired tissue remodelling.
Insights
Cigarette smoke alters lung macrophage populations, increasing specific subtypes and impacting tissue repair. This research clarifies how smoke exposure affects these immune cells and their role in lung inflammation and remodeling.
Area of Science:
- Immunology
- Pulmonary Medicine
- Toxicology
Background:
- Pulmonary macrophages are key in lung inflammation, but their subpopulations' response to cigarette smoke is unclear.
- Cigarette smoke is a major cause of lung disease, involving complex inflammatory processes.
- Understanding macrophage dynamics in smoke-exposed lungs is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the impact of cigarette smoke on pulmonary macrophage subpopulations in mice.
- To determine the mechanisms driving macrophage accumulation, including proliferation and recruitment.
- To assess the functional consequences of smoke-induced macrophage alterations on lung tissue remodeling.
Main Methods:
- Whole-body cigarette smoke exposure in C57BL/6 mice.
- Flow cytometry to analyze macrophage subpopulations.
- Bromodeoxyuridine labeling and genetic models (Il1a, Il1r1) to study macrophage turnover.
- Bleomycin-induced lung injury model to assess tissue remodeling.
Main Results:
- Cigarette smoke exposure increased CD11b+ macrophage subpopulations, including monocyte-derived alveolar macrophages (Mo-AM) and interstitial macrophages (IM).
- IL-1α signaling mediated the increased turnover of Mo-AM and IM3 in smoke-exposed mice.
- Macrophage compositional changes were linked to attenuated fibrogenesis and impaired tissue remodeling following bleomycin injury.
- Predominant M1 macrophage polarization and reduced matrix metallopeptidase 9 activity were observed.
Conclusions:
- Cigarette smoke exposure significantly alters pulmonary macrophage composition by expanding CD11b+ subpopulations.
- These alterations are associated with attenuated fibrogenesis and impaired tissue remodeling.
- The findings suggest a role for altered macrophage subpopulations in the pathogenesis of smoke-induced lung damage.
