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Macrophages pp 299–313Cite as

Macrophage Dysfunction in Respiratory Disease

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Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 62))

Abstract

In the healthy lung, macrophages maintain homeostasis by clearing inhaled particles, bacteria, and removing apoptotic cells from the local pulmonary environment. However, in respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis, macrophages appear to be dysfunctional and may contribute to disease pathogenesis. In COPD, phagocytosis of bacterial species and apoptotic cells by both alveolar macrophages and monocyte-derived macrophages is significantly reduced, leading to colonization of the lung with pathogenic bacteria. COPD macrophages also release high levels of pro-inflammatory cytokines and chemokines, including CXCL8, TGFβ, and CCL2, driving recruitment of other inflammatory cells including neutrophils and monocytes to the lungs and promoting disease progression.

In asthma, defective phagocytosis and efferocytosis have also been reported, and macrophages appear to have altered cell surface receptor expression; however, it is as yet unclear how this contributes to disease progression but may be important in driving Th2-mediated inflammation. In cystic fibrosis, macrophages also display defective phagocytosis, and reduced bacterial killing, which may be driven by the pro-inflammatory environment present in the lungs of these patients.

The mechanisms behind defective macrophage function in lung diseases are not currently understood, but potential mechanisms include alterations in phagocytic receptor expression levels, oxidative stress, but also the possibility that specific diseases are associated with a specific, altered, macrophage phenotype that displays reduced function. Identification of the mechanisms responsible may present novel therapeutic opportunities for treatment.

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Authors and Affiliations

  1. Department of Airway Disease, National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK

    Kylie B. R. Belchamber & Louise E. Donnelly

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  1. Kylie B. R. Belchamber
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  2. Louise E. Donnelly
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Correspondence to Louise E. Donnelly .

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  1. Department of Surgery, The Houston Methodist Hospital, Houston, Texas, USA

    Malgorzata Kloc

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Belchamber, K.B.R., Donnelly, L.E. (2017). Macrophage Dysfunction in Respiratory Disease. In: Kloc, M. (eds) Macrophages. Results and Problems in Cell Differentiation, vol 62. Springer, Cham. https://doi.org/10.1007/978-3-319-54090-0_12

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