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Alternatively activated macrophages and airway disease.

ABSTRACT: Macrophages are the most abundant immune cell population in normal lung tissue and serve critical roles in innate and adaptive immune responses as well as the development of inflammatory airway disease. Studies in a mouse model of chronic obstructive lung disease and translational studies of humans with asthma and COPD have shown that a special subset of macrophages is required for disease progression. This subset is activated by an alternative pathway that depends on production of IL-4 and IL-13, in contrast to the classic pathway driven by interferon-γ. Recent and unexpected results indicate that alternatively activated macrophages (AAMs) can also become a major source of IL-13 production and, thereby, drive the increased mucus production and airway hyperreactivity that is characteristic of airway disease. Although the normal and abnormal functions of AAMs are still being defined, it is already apparent that markers of this immune cell subset can be useful to guide stratification and treatment of patients with chronic airway diseases. Here, we review basic and clinical research studies that highlight the importance of AAMs in the pathogenesis of asthma, COPD, and other chronic airway diseases.

SUBMITTER: Byers DE

PROVIDER: S-EPMC3168852 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Alternatively activated macrophages

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Elimination of classically-activated macrophages in tumor-conditioned medium by alternatively-activated macrophages.

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Project description:Matrix metalloproteinase-10 (MMP-10) is expressed by macrophages and epithelium in response to injury, but its functions in wound repair are unknown. We observed increased collagen deposition and skin stiffness in Mmp10(-/-) wounds, with no difference in collagen expression or reepithelialization. Increased collagen deposition in Mmp10(-/-) wounds was accompanied by less collagenolytic activity and reduced expression of specific metallocollagenases, particularly MMP-8 and MMP-13, where MMP-13 was the key collagenase. Ablation and adoptive transfer approaches and cell-based models demonstrated that the MMP-10-dependent collagenolytic activity was a product of alternatively activated (M2) resident macrophages. These data demonstrate a critical role for macrophage MMP-10 in controlling the tissue remodeling activity of macrophages and moderating scar formation during wound repair.

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