M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other monocyte/macrophage subtypes
| Autor: | Keith Morris, Richard Webb, SA Isa, A. W. Thomas, Maninder Ahluwalia, Jose Sofia Ruffino |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Genetic Markers
X-Box Binding Protein 1 Clinical chemistry Cell Survival Endocrinology Diabetes and Metabolism Primary Cell Culture Clinical Biochemistry Gene Expression Apoptosis Receptors Cell Surface Regulatory Factor X Transcription Factors UPR Biology Endocrinology Heat shock protein Macrophage Humans Lectins C-Type Obesity Receptor Endoplasmic Reticulum Chaperone BiP lcsh:RC620-627 Cells Cultured Heat-Shock Proteins alternative M2 monocyte/macrophage polarisation Biochemistry medical oxLDL Macrophages Research Biochemistry (medical) Cell Polarity lipotoxicity Endoplasmic Reticulum Stress Phenotype DNA-Binding Proteins Lipoproteins LDL Interleukin 1 Receptor Antagonist Protein lcsh:Nutritional diseases. Deficiency diseases Mannose-Binding Lectins Lipotoxicity Cell culture Immunology Calcium Mannose Receptor Transcription Factor CHOP Transcription Factors |
| Zdroj: | Lipids in Health and Disease, Vol 10, Iss 1, p 229 (2011) Lipids in Health and Disease |
| Popis: | Background In obesity, phenotypic switches occur in macrophage populations such that the predominantly M2-polarised anti-inflammatory state seen in lean individuals changes to a predominantly M1-polarised pro-inflammatory state in those who are obese. However, the mechanisms by which these phenotypic shifts occur have not yet been fully elucidated. Results The effects of oxLDL (1-40 μg/ml; 24 h) on several parameters relevant to the Unfolded Protein Response (UPR)-mediated lipotoxic effects of oxLDL (disruption of ER Ca2+ handling; activation of the UPR transcription factor XBP-1; upregulation of the UPR target genes BiP and CHOP; apoptosis; cell viability) were investigated in human primary monocyte-derived macrophages, and also in monocyte-macrophages derived from the THP-1 monocytic cell line. A consistent pattern was observed: M2-polarised macrophages were more sensitive to the lipotoxic effects of oxLDL than either non-polarised macrophages or non-differentiated monocytic cells. Specifically, M2-polarised macrophages were the only cell type to undergo significantly increased apoptosis (Primary cells: 1.23 ± 0.01 basal; THP-1-derived: 1.97 ± 0.12 basal; P < 0.05 in both cases) and decreased cell viability (Primary cells: 0.79 ± 0.04 basal; THP-1-derived: 0.67 ± 0.02 basal; P < 0.05 in both cases) when exposed to oxLDL levels similar to those seen in overweight individuals (ie. 1 μg/ml). Conclusions We propose that the enhanced susceptibility of M2-polarised macrophages to lipotoxicity seen in the present in vitro study could, over time, contribute to the phenotypic shift seen in obese individuals in vivo. This is because a higher degree of oxLDL-induced lipotoxic cell death within M2 macrophages could contribute to a decrease in numbers of M2 cells, and thus a relative increase in proportion of non-M2 cells, within macrophage populations. Given the pro-inflammatory characteristics of a predominantly M1-polarised state, the data presented here may constitute a useful contribution to our understanding of the origin of the pro-inflammatory nature of obesity, and of the pathogenesis of obesity-associated inflammatory disorders such as Type 2 Diabetes and atherosclerosis. |
| Databáze: | OpenAIRE |
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