Biology of macrophage fate decision: Implication in inflammatory disorders

Abstract

The activation of immune cells in response to stimuli present in their microenvironment is regulated by their metabolic profile. Unlike the signal transduction events, which overlap to a huge degree in diverse cellular processes, the metabolome of a cell reflects a more precise picture of cell physiology and function. Different factors governing the cellular metabolome include receptor signaling, macro and micronutrients, normoxic and hypoxic conditions, energy needs, and biomass demand. Macrophages have enormous plasticity and can perform diverse functions depending upon their phenotypic state. This review presents recent updates on the cellular metabolome and molecular patterns associated with M1 and M2 macrophages, also termed “classically activated macrophages” and “alternatively activated macrophages,” respectively. M1 macrophages are proinflammatory in nature and predominantly Th1‐specific immune responses induce their polarization. On the contrary, M2 macrophages are anti‐inflammatory in nature and primarily participate in Th2‐specific responses. Interestingly, the same macrophage cell can adapt to the M1 or M2 phenotype depending upon the clues from its microenvironment. We elaborate on the various tissue niche‐specific factors, which govern macrophage metabolism and heterogeneity. Furthermore, the current review provides an in‐depth account of deregulated macrophage metabolism associated with pathological disorders such as cancer, obesity, and atherosclerosis. We further highlight significant differences in various metabolic pathways governing the cellular bioenergetics and their impact on macrophage effector functions and associated disorders.

Modulation of Retinal Inflammation Delays Degeneration in a Mouse Model of Geographic Atrophy

“…Monocytic cells (e.g., microglia, macrophages, and monocytes) are known to express genes involved in either an active inflammatory response (M1 phenotype) or pro-angiogenesis response (M2 phenotype), which are considered anti-inflammatory 28 . To determine how retinal M013 expression impacts the levels of either M1 or M2-associated genes, we used RT-qPCR in retina RNA samples to measure gene expression changes.…”

“…Therefore, frozen sections from animals treated with either sGFP or sGFP-TatM013v5 vector were sectioned and stained with anti-CD45 antibody to detect the presence of immune cells within the retina. In sections of three-month-old mice, there were CD45 positive cells in all the ONL and subretinal space only in sGFP-treated eyes (Fig 4A Monocytic cells (e.g., microglia, macrophages, and monocytes) are known to express genes involved in either an active inflammatory response (M1 phenotype) or pro-angiogenesis response (M2 phenotype), which are considered anti-inflammatory 28 . To determine how retinal M013 expression impacts the levels of either M1 or M2-associated genes, we used RT-qPCR in retina RNA samples to measure gene expression changes.…”

MCP-1-Loaded Poly(l-lactide-co-caprolactone) Fibrous Films Modulate Macrophage Polarization toward an Anti-inflammatory Phenotype and Improve Angiogenesis

“…Electrospinning by biodegradable polymers is a promising approach to fabricating bionic small-diameter vascular scaffolds. ,,,, Particularly, coaxial electrospinning can encapsulate bioactive components in polymer materials that can provide vascular scaffolds with favorable mechanical and biological properties. , Although significant amounts of research have focused on developing electrospinning small-diameter vascular scaffolds in recent years, the implanted scaffolds are still challenged by FBR in scaffold remodeling, leading to graft failure. ,, After scaffold implantation, macrophages are involved in nearly every biological process. , Currently, several studies have focused on the interaction between biomaterial scaffolds and macrophages to reduce FBR by regulating macrophage polarization, for instance, through surface modification and cytokine loading. ,,, …”

“…24,29,49 After scaffold implantation, macrophages are involved in nearly every biological process. 30,50 Currently, several studies have focused on the interaction between biomaterial scaffolds and macrophages to reduce FBR by regulating macrophage polarization, for instance, through surface modification and cytokine loading. 27,34,35,51 MCP-1 is a major monocyte chemotactic cytokine that induces the recruitment of macrophages through interaction with CCR2.…”

“…Macrophages play a pivotal role in scaffold remodeling via specific functional polarization. Macrophages typically demonstrate two distinct phenotypes: classically activated macrophages (M1) and alternatively activated macrophages (M2). − M1 macrophages are generally considered to be pro-inflammatory and stimulate angiogenesis at an early stage after scaffold implantation . On the other hand, M2 macrophages have anti-inflammatory properties that inhibit inflammation by secreting anti-inflammatory cytokines and stabilizing angiogenesis. , …”