Tissue-Specific Role of Macrophages in Noninfectious Inflammatory Disorders

Abstract

Chronic inflammation may not begin with local tissue disorders, such as hypoxia, but with the accumulation of critically activated macrophages in one site. The purpose of this review is to analyze the data reported in the scientific literature on the features of the functions of macrophages and their contributions to the development of pathology in various tissues during aseptic inflammation in obese subjects. In individuals with obesity, increased migration of monocytes from the peripheral blood to various tissues, the proliferation of resident macrophages and a change in the balance between alternatively activated anti-inflammatory macrophages (M2) and pro-inflammatory classically activated macrophages (M1) towards the latter have been observed. The primary cause of some metabolic pathologies has been precisely identified as the recruitment of macrophages with an altered phenotype, which is probably typical for many other pathologies. Recent studies have identified phenotypes, such as metabolically activated M (MMe), oxidized (Mox), hemoglobin-related macrophages (Mhem and MHb), M4 and neuroimmunological macrophages (NAM, SAM), which directly and indirectly affect energy metabolism. The high heterogeneity of macrophages in tissues contributes to the involvement of these cells in the development of a wide range of immune responses, including pathological ones. The replenishment of tissue-specific macrophages occurs at the expense of infiltrating monocyte-derived macrophages (MoMFs) in the pathological process. The origin of MoMFs from a general precursor retains their common regulatory mechanisms and similar sensitivity to regulatory stimuli. This makes it possible to find universal approaches to the effect on these cells and, as a consequence, universal approaches for the treatment of various pathological conditions.

Roles of Macrophages in Atherogenesis

“…Following endocytosis of hemoglobin-haptoglobin complex, heme is released from RBCs which stimulates Mφ polarization to human atheroprotective Mhem subtype implicated in erythrophagocytosis. The Mhem Mφ suppressed OS, lipid accumulation, and foam cell formation, sharing properties with M (Hb) (Skuratovskaia et al, 2020).…”

“…They can be involved in fibrous cap degradation, and plaque rupture by producing the enzyme MMP12. M4 Mφ also seems to be irreversible and can not switch like M1, M2, or hemorrhage-associated phenotypes (Skuratovskaia et al, 2020).…”

“…M4 Mφs are induced by CXCL-4 in human atherosclerotic plaques. M4 Mφs have pro-inflammatory and proatherogenic properties which may develop in arterial thrombosis (Skuratovskaia et al, 2020). M4 Mφs are unable to efficiently phagocytose Ox-LDL, with minimal formation of foam cells, and also may not function as efferocytes within plaques (Butcher and Galkina, 2012).…”

“…Neuroimmunological Mφs may have therapeutic potential for individuals with obesity (Skuratovskaia et al, 2020).…”

Macrophages in Health and Non-Infectious Disease

“…Skuratovskaia with coauthors [ 23 ] reviewed the idea that chronic inflammation is related to the accumulation of critically activated macrophages in one site with a focus on obesity. The authors analyzed the data from the scientific publications on macrophages and their involvement in the pathogenesis in different tissues during aseptic inflammation in obese individuals.…”