Characterisation of lung macrophage subpopulations in COPD patients and controls

Abstract

Lung macrophage subpopulations have been identified based on size. We investigated characteristics of small and large macrophages in the alveolar spaces and lung interstitium of COPD patients and controls. Alveolar and interstitial cells were isolated from lung resection tissue from 88 patients. Macrophage subpopulation cell-surface expression of immunological markers and phagocytic ability were assessed by flow cytometry. Inflammatory related gene expression was measured. Alveolar and interstitial macrophages had subpopulations of small and large macrophages based on size and granularity. Alveolar macrophages had similar numbers of small and large cells; interstitial macrophages were mainly small. Small macrophages expressed significantly higher cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large macrophages. Large alveolar macrophages showed lower marker expression in COPD current compared to ex-smokers. Small interstitial macrophages had the highest pro-inflammatory gene expression levels, while large alveolar macrophages had the lowest. Small alveolar macrophages had the highest phagocytic ability. Small alveolar macrophage CD206 expression was lower in COPD patients compared to smokers. COPD lung macrophages include distinct subpopulations; Small interstitial and small alveolar macrophages with more pro-inflammatory and phagocytic function respectively, and large alveolar macrophages with low pro-inflammatory and phagocytic ability.

Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1

“…CMPs integrate in the toponome, which combines aspects of the proteome and the interactome, and this study reflects the assembly and/or interactions of the 13 markers in a given cellular space in intact cells. As pointed out in the Background, the AM cell population is known to have a high degree of phenotypic diversity [12,31,32,50]. Hence the finding of heterogeneity identified in this study is, in itself, not surprising.…”

Efficient and specific Ly6G+cell depletion: A change in the current practices toward more relevant functional analyses of neutrophils

“…IM showed a lower expression of tumor-promoting genes such as Mmp9 33 and immunomodulatory mediators (Arg1, Nos2). Hence, neutrophil infiltration might link some of the alterations reported on lung tumor patients' AMs [34][35][36] . Finally, treating KP mice with anti-Ly6G ab alone failed to demonstrate any effect on tumor growth and the immune signature.…”

Basophils trigger emphysema development in a murine model of COPD through IL-4–mediated generation of MMP-12–producing macrophages

“…Moreover, cigarette smoke reportedly increased the accumulation of CX3CR1 + CD11b + mononuclear phagocytes that are spatially confined to the lung interstitium, and mice deficient for CX3CR1 showed protection from emphysema formation (35), suggesting the important role of IMs in smoke-induced COPD as well. Intriguingly, gene expression profiling in lung samples isolated from COPD patients revealed that IMs display a higher proinflammatory signature than AMs (36), suggesting the possible role of IMs rather than AMs in the pathogenesis of human COPD as identified in the mouse model.…”