Macrophages and Inflammatory Mediators in Chemical Toxicity: A Battle of Forces

Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, New Jersey 08854.
Chemical Research in Toxicology (Impact Factor: 4.19). 08/2009; 22(8):1376-85. DOI: 10.1021/tx900086v
Source: PubMed

ABSTRACT Macrophages function as control switches of the immune system, providing a balance between pro- and anti-inflammatory responses. To accomplish this, they develop into different subsets: classically (M1) or alternatively (M2) activated macrophages. Whereas M1 macrophages display a cytotoxic, proinflammatory phenotype, much like the soldiers of The Dark Side of The Force in the Star Wars movies, M2 macrophages, like Jedi fighters, suppress immune and inflammatory responses and participate in wound repair and angiogenesis. Critical to the actions of these divergent or polarized macrophage subpopulations is the regulated release of inflammatory mediators. When properly controlled, M1 macrophages effectively destroy invading pathogens, tumor cells, and foreign materials. However, when M1 activation becomes excessive or uncontrolled, these cells can succumb to The Dark Side, releasing copious amounts of cytotoxic mediators that contribute to disease pathogenesis. The activity of M1 macrophages is countered by The Force of alternatively activated M2 macrophages, which release anti-inflammatory cytokines, growth factors, and mediators involved in extracellular matrix turnover and tissue repair. It is the balance in the production of mediators by these two macrophage subpopulations that ultimately determines the outcome of the tissue response to chemical toxicants.

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    • "Thus, breast cancer associated macrophages likely enhance matrix deposition, remodeling, and the formation/recruitment of new blood vessels. Furthermore, macrophages regulate innate and adaptive immune responses via various mechanisms that include phagocytosis, free radical production, and the professional presentation of antigen to T cell subsets (Laskin, 2009). The cytokine, TGF-β, which is produced by tumor cells and fibroblasts (Kojima et al., 2010; Margadant and Sonnenberg, 2010), down-regulates macrophage free radical production and the expression of co-stimulatory molecules required for antigen presentation (Li et al., 2006). "
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    • "The M1 types are induced by inflammatory agents, whereas M2 types are induced by IL-4 and IL-13 (Zeyda et al., 2007). The M1-type macrophages display a cytotoxic, proinflammatory phenotype, whereas M2-type macrophages suppress immune and inflammatory responses and participate in wound repair and angiogenesis (Laskin, 2009). The ATM phenotypically resemble the antiinflammatory M2 type of macrophage in humans and mice (Zeyda and Stulnig, 2007). "
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