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Induction of murine macrophage growth by modified LDLs
1Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Abstract:
We previously reported that cell membrane components and lipoproteins were able to induce the growth of murine peritoneal macrophages. The aim of the present study was to examine whether macrophage growth could also be induced by chemically modified lipoproteins, such as acetylated low density lipoprotein (acetyl-LDL) or oxidized LDL, ligands known to be endocytosed by the macrophage scavenger receptors. When murine peritoneal exudate macrophages were cultured in vitro with 25-100 micrograms/mL acetyl-LDL or oxidized LDL, significant growth was induced. On comparing the dose-response curves of these LDLs, a more potent effect was seen with oxidized LDL than acetyl-LDL, especially on resident macrophages. On the other hand, growth of these cells was not stimulated by native (unmodified) LDL or high density lipoprotein. These in vitro data revealed a new function of chemically modified LDLs as effective inducers of macrophage cell growth. This aspect may be physiologically relevant to the growth of macrophage foam cells in situ in the development of atherosclerosis.
Insights
Chemically modified lipoproteins, like acetylated LDL and oxidized LDL, significantly induce macrophage growth. Oxidized LDL shows a stronger effect, potentially impacting foam cell development in atherosclerosis.
Area of Science:
- Immunology
- Cell Biology
- Cardiovascular Research
Background:
- Macrophages play a crucial role in immune responses and tissue homeostasis.
- Lipoproteins, particularly low-density lipoprotein (LDL), are implicated in atherosclerosis.
- Previous work indicated cell membrane components and lipoproteins stimulate macrophage growth.
Purpose of the Study:
- To investigate if chemically modified lipoproteins, specifically acetylated LDL and oxidized LDL, can induce macrophage growth.
- To compare the growth-inducing potency of acetyl-LDL and oxidized LDL on murine peritoneal macrophages.
- To determine if native LDL or high-density lipoprotein (HDL) also stimulate macrophage growth.
Main Methods:
- Murine peritoneal exudate macrophages were cultured in vitro.
- Macrophages were treated with varying concentrations (25-100 µg/mL) of acetyl-LDL and oxidized LDL.
- Dose-response curves were generated to compare the effects of different LDL modifications and native lipoproteins.
Main Results:
- Both acetyl-LDL and oxidized LDL significantly induced macrophage growth in vitro.
- Oxidized LDL demonstrated a more potent growth-inducing effect than acetyl-LDL, particularly on resident macrophages.
- Native LDL and HDL did not stimulate macrophage growth.
Conclusions:
- Chemically modified LDLs, including acetyl-LDL and oxidized LDL, are effective inducers of macrophage cell growth.
- This finding suggests a novel function for modified LDLs in regulating macrophage proliferation.
- The observed macrophage growth induction may be physiologically relevant to the development of macrophage foam cells in atherosclerosis.