Macrophage Heterogeneity 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


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
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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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    Frontiers in Immunology 09/2014; 5:430. DOI:10.3389/fimmu.2014.00430
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    • "M2 polarization encompasses at least two subtypes M2 and M2-like macrophages dependent on the cytokine milieu macrophages are subjected to. M2 macrophages differentiate in response to IL-4 and IL-13 whereas M2-like macrophages acquire their phenotype in response to TGF-b, IL-10 or PGE and additional TLR activation [6]. M2-like macrophages release high amounts of IL-10 and are thus considered to be anti-inflammatory. "
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    ABSTRACT: The role of M2 polarized macrophages (MPhi) during the allergic airway inflammation has been discussed in various animal models. However, their presence and relevance during the chronic and acute phase of allergic airway inflammation in humans has not been fully elucidated so far. In the present study we phenotypically characterized macrophages with regard to M2 polarization in mice, a human in vitro and a human ex vivo model with primary lung cells after endobronchial provocation. Macrophages remained polarized beyond clearance of the acute allergic airway inflammation in mice. Alveolar macrophages of asthmatics revealed increased mRNA expression of CCL13, CCL17 and CLEC10A in response to allergen challenge as well as increased surface expression of CD86. Further, mRNA expression of CCL13, CCL17, and CLEC10A was increased in asthmatics at baseline compared to healthy subjects. The mRNA expression of CCL17 and CLEC10A correlated significantly with the degree of eosinophilia (each P < .01). Furthermore, macrophages from asthmatics released significant amounts of CCL17 protein in vitro which was also found increased in BAL fluid after allergen provocation. This study supports previous findings of M2 macrophage polarization in asthmatic subjects during the acute course of the allergic inflammation and provides evidence for their contribution to the Th2 inflammation.
    BMC Immunology 03/2014; 15(1):12. DOI:10.1186/1471-2172-15-12 · 2.48 Impact Factor
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    • "M2 macrophages have been found to correlate with the severity of allergic airway inflammation in human and mice. M1 macrophages have been suggested to be beneficial to prevent allergic sensitization but may promote development of M2 macrophages in the presence of established disease (5). In OVA-challenged mice, an increase in macrophages were recovered in the BAL fluid following 1 week of OVA challenge, compared to saline control mice. "
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