Macrophages: Master Regulators of Inflammation and Fibrosis

By TA Wynn, Luke Barron. Seminars in liver disease (Print), 2010

1,385 citations recorded by the source corpus.

Macrophages are found in close proximity with collagen-producing myofibroblasts and indisputably play a key role in fibrosis. They produce profibrotic mediators that directly activate fibroblasts, including transforming growth factor-β1 and platelet-derived growth factor, and control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. Macrophages also regulate fibrogenesis by secreting chemokines that recruit fibroblasts and other inflammatory cells. With their potential to act in both a pro- and antifibrotic capacity, as well as their ability to regulate the activation of resident and recruited myofibroblasts, macrophages and the factors they express are integrated into all stages of the fibrotic process. These various, and sometimes opposing, functions may be performed by distinct macrophage subpopulations, the identification of which is a growing focus of fibrosis research. Although collagen-secreting myofibroblasts once were thought of as the master “producers” of fibrosis, this review will illustrate how macrophages function as the master “regulators” of fibrosis.

Subfields: Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/1523e4f6adf336014b0aabe2c7f8ec020363fcf3

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In Cardiology and Cardiovascular Medicine

TA Wynn

In Pulmonary and Respiratory Medicine

Citations in the corpus

Macrophage phenotypes during tissue repair (2013, neutral): “likely context-dependent [39–41].”
Chronic Wound Healing: A Review of Current Management and Treatments (2017, background): “A complex interplay of cytokines also helps to regulate this phase, culminating in monocyte conversion to macrophages, often thought of as the master regulator of this inflammatory phase of wound healing [5].”
Protective and pathogenic functions of macrophage subsets (2011, background): “In addition to their innate phagocytic activity and role in antimicrobial immunity, macrophages are intimately involved in wound repai”
Mechanisms of fibrosis: therapeutic translation for fibrotic disease (2012, neutral): “A unique functional subset of macrophages, called M2 or alternatively activated macrophages, has also been implicated in the pathogenesis of fibrosis 39 .”
The Pathogenesis of Cardiac Fibrosis (2013, neutral): “Monocytes and macrophages not only play important roles in initiation and progression of fibrotic responses, but may also mediate resolution of fibrosis [55].”
Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine (2012, background): “Persistent or dysregulated inflammation can result in fibrosis following tissue injury or in the setting of infection [101,102].”
Host Responses in Tissue Repair and Fibrosis (2012, background): “Indeed, conditional ablation of macrophages at early stages of fibrosis blocks fibrosis progression in several fibrosis model systems (4, 206, 218).”
Aberrant repair and fibrosis development in skeletal muscle (2011, background): “A nomenclature for polarized macrophages has been proposed [24,25] and they are now referred to as classically and alternatively activated macrophages, or M1 and M2 macrophages, respectively (Figure 2, Figure 3).”
Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils (2011, background): “Tissue macrophages differentiate from circulating monocytes when they enter tissues and are distinguished from DCs by their expression of F4/80, CD11b and Fc receptors; also, in contrast to DCs, which serve as the main inducers of adaptive T cell responses, macrophages have proteolytic and catabolic”
Integrating mechanisms of pulmonary fibrosis (2011, background): “Disease stage-specific roles of macrophages Macrophages are integrated into all stages of the fibrotic process, perhaps because they serve as key regulators of fibroblast recruitment, proliferation, and activation (Wynn and Barron, 2010).”
Skin Acute Wound Healing: A Comprehensive Review (2019, background): “Simultaneously, an active paracrine interaction between keratinocytes, fibroblasts, neutrophils, monocytes-macrophages, and endothelial cells increases the amount of cytokines, growth factors, and other biomolecules to promote the epithelial-mesenchymal interaction between keratinocytes and fibrobla”