Heterogeneity of Human Macrophages in Culture and in Atherosclerotic Plaques

Abstract

Research suggests that monocytes differentiate into unique lineage-determined macrophage subpopulations in response to the local cytokine environment. The present study evaluated the atherogenic potential of two divergent lineage-determined human monocyte-derived macrophage subpopulations. Monocytes were differentiated for 7 days in the presence of alternative macrophage development cytokines: granulocyte-macrophage colony-stimulating factor to produce granulocyte-macrophage-CSF macrophages (

Microenviromental factors controlling macrophage polarization in atherosclerosis

“…In mouse and human lesions, M-CSF is detected both in healthy arteries and atherosclerotic lesions, and in the latter is associated with macrophage and foam-cell content and correlates with plaque progression [8,21,22,34]. These data are consistent with a scenario in which M-CSF and GM-CSF both contribute to macrophage heterogeneity observed in plaques.…”

“…M-CSF upregulates enzymes involved in cholesterol biosynthesis and downregulates ATP-binding cassette transporter G1 (ABCG1), which is involved in cholesterol efflux. Moreover, in human monocyte-derived macrophages, oxLDL accumulation is higher in M-CSF-differentiated macrophages than in GM-CSF-differentiated cells, and correlates with the upregulation of CD36 and SR-A, membrane proteins involved in the uptake of modified lipids [8,22].…”

“…However, GM-CSF + macrophages (CD68 + CD14 -according to Waldo et al) seem to constitute only a minor fraction of atherosclerotic macrophages, and indeed GM-CSF is not always detected in human atherosclerotic lesions [22].…”

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

“…For example, classically activated macrophages exposed to IFNγ and microbial products such as LPS during bacterial infection are critical for efficient immune responses while alternatively activated macrophages have been shown to be important in the resolution of inflammation [37,38]. Both macrophage sub-phenotypes have been identified in human atherosclerosis and have been found to localize to unique areas of the plaque suggesting that they are involved in different processes [9,39,40]. Because of these differences in function, we sought to compare the ability of established macrophage sub-phenotypes to maintain cholesterol homeostasis.…”

Enhanced Expression of Hemoglobin Scavenger Receptor CD163 in Accumulated Macrophages Within Filtered Debris Between Acute Coronary Syndromes and Stable Angina Pectoris

“…2) CD14 on the macrophage surface is bound to lipopolysaccharides, thereby activating macrophages to produce cytokines such as TNF-α, IL-1, and IL-6, which, in turn, serve as endogenous mediators of inflammation. 3) In a previous pathological report, CD14-positive macrophages were more prevalent in atherosclerotic lesions compared with normal intimal regions of coronary arteries.…”