Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein

Abstract

LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-α and IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis.

N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

“…As anticipated, MPO expression is predominantly observed in the neutrophil fraction and to a lesser degree in the monocytes fraction which is consistent with prior observations [41] Future studies will characterize the cell frequency in AIED patients, as neither we, or other investigators have determined if any irregularities exist. Others have shown that MPO is important in LDL oxidation and resultant monocyte differentiation into classical or alteratively activated macrophages based on the amount of oxidized LDL [42], suggesting that MPO activity may dictate monocyte differentiation and disease progression or remission in other systems based on the local microenvironment. It is certainly possible that prolonged treatment with NAC may improve MPO repression.…”

Relationship Between Lipid Assessment and Arterial Lesions Observed in Farm Chickens Fed on Different Vegetable Oils

“…As the main part of LDL, cholesteryl esters might provide polyunsaturated fatty acids (PUFA) to cells efficiently via LDL receptor. It was assumed that PUFA in cholesteryl esters were closely correlated with the cholesterol metabolism and the atherosclerosis development by regulating the LDL receptor activity, the platelet function and the prostaglandin synthesis [20,21]. There is evidence that oxidatively modified LDL plays a crucial role in atherogenesis [22,23].…”

“…The pathological examinations for chickens arteries fed on the various varieties of palm oil were carried out in the arteries, such aorta, coronary arteries and cerebral arteries, which are the usual sites of predilection for the atherosclerosis [21]. The main goal of this pathological study was to determine a possible relationship between various oils and arterial lesions observed in these arteries.…”

Regulation mechanism of PDK1 on macrophage metabolism and function

“…The lipid oxidation level of LDL is important for macrophage differentiation as indicated by a recent study. Also, hi‐oxLDL is beneficial for M2 macrophages while low‐oxLDL is beneficial for M1 macrophage . Numerous signaling proteins contribute to the regulation of macrophages, and most of them are related to the PDK1.…”

“…Also, hi-oxLDL is beneficial for M2 macrophages while low-oxLDL is beneficial for M1 macrophage. 34 Numerous signaling proteins contribute to the regulation of macrophages, and most of them are related to the PDK1. So the important role played by PDK1 in macrophage function cannot be ignored.…”