Article

Macrophage Heterogenity in Respiratory Diseases

Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
Mediators of Inflammation (Impact Factor: 3.24). 02/2013; 2013(7):769214. DOI: 10.1155/2013/769214
Source: PubMed

ABSTRACT

Macrophages are among the most abundant cells in the respiratory tract, and they can have strikingly different phenotypes within this environment. Our knowledge of the different phenotypes and their functions in the lung is sketchy at best, but they appear to be linked to the protection of gas exchange against microbial threats and excessive tissue responses. Phenotypical changes of macrophages within the lung are found in many respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. This paper will give an overview of what macrophage phenotypes have been described, what their known functions are, what is known about their presence in the different obstructive and restrictive respiratory diseases (asthma, COPD, pulmonary fibrosis), and how they are thought to contribute to the etiology and resolution of these diseases.

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Available from: Barbro Melgert, Mar 13, 2014
    • "Increased levels of activated STAT4 (Di Stefano et al., 2004) and diminished production of IL10 were reported in patients with acute inflammation of COPD and bronchial asthma (Hackett et al., 2008;Takanashi et al., 1999). These observations suggest impaired functions of specialized cells, such as interstitial macrophages that produce IL10 and offer the first line of defense against allergens and toxic insults; as a result, lung homeostasis can be compromised (Boorsma et al., 2013). In a previous study we have reported the main effects (HertzPicciotto et al., 2007) of polycyclic aromatic hydrocarbons (PAH) and particulate matter b 2.5 μm (PM 2.5 ) on risk for bronchitis in children. "
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    • "Oxidative stress further amplified the inflammation, resulting in frequent COPD exacerbations. One of the key inflammatory cells during COPD are macrophages existing in airway lumen, lung parenchyma and broncoalveolar lavage fluid [11]. These macrophages, the major component of innate immune response, control the functions of T-lymphocytes and the production of pro-/antiinflammatory cytokines, determining AECOPD and the progression of the disease [12]. "

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    • "Since the number of IRF-5+ (M1-dominant) macrophages was almost unchanged in fibrotic livers compared to livers undergoing resolution, we measured MMP expression as a functional read out of the presence of these macrophages. M1-dominant cells are known to express MMP9 (17, 21, 36, 37) and western blot analysis of these livers revealed significantly higher expression of MM9 92 kDa, which is known as pro-MMP9, and its processed form (67 kDa MMP9) in the livers undergoing resolution (Figure 10F). "
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    ABSTRACT: Macrophages have been found to both promote liver fibrosis and contribute to its resolution by acquiring different phenotypes based on signals from the micro-environment. The best-characterized phenotypes in the macrophage spectrum are labeled M1 (classically activated) and M2 (alternatively activated). Until now the in situ localization of these phenotypes in diseased livers is poorly described. In this study, we therefore aimed to localize and quantify M1- and M2-dominant macrophages in diseased mouse and human livers. The scarred collagen-rich areas in cirrhotic human livers and in CCl4-damaged mouse livers contained many macrophages. Though total numbers of macrophages were higher in fibrotic livers, the number of parenchymal CD68-positive macrophages was significantly lower as compared to normal. Scar-associated macrophages were further characterized as either M1-dominant (IRF5 and IL-12) or M2-dominant (CD206, TGM2 and YM-1) and significantly higher numbers of both of these were detected in diseased livers as compared to healthy human and mouse livers. Interestingly, in mouse livers undergoing resolution of fibrosis, the total number of CD68+ macrophages was significantly lower compared to their fibrotic counterparts. M2-dominant (YM-1) macrophages were almost completely gone in livers undergoing resolution, while numbers of M1-dominant (IRF5) macrophages were unchanged and the proteolytic activity (MMP9) increased. In conclusion, this study shows the distribution of macrophage subsets in livers of both human and murine origin. The presence of M1-and M2-dominant macrophages side by side in fibrotic lesions suggests that both are involved in fibrotic responses, while the persistence of M1-dominant macrophages during resolution may indicate their importance in regression of fibrosis. This study emphasizes that immunohistochemical detection of M1/M2-dominant macrophages provides valuable information in addition to widely used flow cytometry and gene analysis.
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