Alternative Activation of Macrophages: Mechanism and Functions

Abstract

The concept of an alternative pathway of macrophage activation has stimulated interest in its definition, mechanism, and functional significance in homeostasis and disease. We assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment. The stage is now set to gain deeper insights into the role of alternatively activated macrophages in immunobiology.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…Indeed, macrophages control osteogenesis from mesenchymal stem cells, mechanism dependent on Oncostatin M signaling. The role of macrophages present in the vicinity of tumor cells, named "Tumor-Associated Macrophages" (TAMs), has been extensively studied [61][62][63]. [67].…”

Cellular senescence impact on immune cell fate and function

“…Heterogeneity of the macrophage lineage has long been recognized (Gordon & Taylor, 2005), and they have different functional roles depending on their tissue location and the inflammatory environment that drives their activation (Davies et al ., 2013). In this context, macrophage activation has been conventionally categorized into pro‐inflammatory M1 macrophages, induced by IFN‐γ and toll‐like receptor (TLR) ligands, and the alternatively activated anti‐inflammatory M2 macrophages, induced by IL‐4/IL‐13 (Biswas & Mantovani, 2010; Gordon & Martinez, 2010). M1 are efficient producers of toxic effector molecules, pro‐inflammatory cytokines, and chemokines that kill pathogens and virus‐infected cells as well as senescent or cancer cells (Hoenicke & Zender, 2012; Davies et al ., 2013).…”

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

“…Due to the high levels of SRs, mannose receptors and galactose-type receptors (Martinez et al, 2006) on their surface, M2 macrophages have a high capacity to phagocytose tissue debris and apoptotic bodies and are able to prevent uncontrolled tissue damage (Gordon and Martinez, 2010). Recent studies have described a third macrophage subtype, Mox, which is found in the oxLDL-rich microenvironment of atherosclerosis.…”