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Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions
J A Berliner1, M C Territo, A Sevanian
1Department of Pathology, University of California, School of Medicine, Los Angeles 90024-1732.
Abstract:
The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.
Insights
Minimally modified LDL (MM-LDL) significantly boosts monocyte-endothelial cell interactions and enhances resistance to MM-LDL toxicity. This study reveals MM-LDL
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- Endothelial cells (EC) play a crucial role in regulating immune cell interactions.
- Modified forms of low-density lipoprotein (LDL) can influence EC function and inflammatory responses.
Purpose of the Study:
- To investigate the impact of minimally modified LDL (MM-LDL) on endothelial cell interactions with monocytes and neutrophils.
- To explore the mechanisms underlying MM-LDL-induced changes in endothelial cell behavior and toxicity.
Main Methods:
- Treatment of large vessel endothelial cells (EC) with MM-LDL preparations.
- Quantification of monocyte and neutrophil binding to EC.
- Assessment of chemotactic factor production by EC.
- Evaluation of MM-LDL toxicity and induced resistance in EC.
Main Results:
- MM-LDL significantly increased monocyte chemotactic factor production and monocyte binding to EC.
- Monocyte binding peaked at 4 hours and persisted for 48 hours.
- Neutrophil binding to EC was not significantly affected by MM-LDL.
- MM-LDL exhibited differential toxicity to EC, with some strains becoming resistant after pre-incubation.
Conclusions:
- Sublethal exposure to MM-LDL enhances monocyte-endothelial cell interactions.
- EC can develop resistance to the toxic effects of MM-LDL.
- These findings highlight a novel mechanism of immune cell modulation by modified lipoproteins.
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