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The scavenger receptor serves as a route for internalization of lysophosphatidylcholine in oxidized low density
M Sakai1, A Miyazaki, H Hakamata
1Department of Metabolic Medicine, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860, Japan. horiuchi@gpo.kumamoto-u.ac.jp
Abstract:
We have recently demonstrated that the growth of murine macrophages is induced by oxidized low density lipoprotein (Ox-LDL) and that lysophosphatidylcholine (lyso-PC), a major phospholipid component of Ox-LDL, plays an essential role in its mitogenic effect. The present study was undertaken to further characterize the role of the macrophage scavenger receptor (MSR) in Ox-LDL-induced macrophage growth. The growth-stimulating effect of Ox-LDL on murine resident peritoneal macrophages was inhibited by maleylated bovine serum albumin (maleyl-BSA), a non-lipoprotein ligand for MSR but a poor carrier of lyso-PC, while maleyl-BSA itself failed to induce macrophage growth even in the presence of lyso-PC. Moreover, it competitively inhibited the endocytic uptake of 125I-Ox-LDL and the specific uptake of lyso-PC by MSR, whereas nonspecific lyso-PC transfer to cells was not affected. Furthermore, the Ox-LDL-induced cell growth of peritoneal macrophages obtained from MSR knockout mice was significantly weaker than that of macrophages obtained from their wild-type littermates. Our results suggest that the MSR is an important and efficient internalization pathway for lyso-PC in Ox-LDL-induced macrophage growth.
Insights
Oxidized low-density lipoprotein (Ox-LDL) induces macrophage growth, with lysophosphatidylcholine (lyso-PC) being key. The macrophage scavenger receptor (MSR) facilitates lyso-PC uptake, driving Ox-LDL-induced macrophage proliferation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Oxidized low-density lipoprotein (Ox-LDL) is known to induce macrophage growth.
- Lysophosphatidylcholine (lyso-PC), a component of Ox-LDL, plays a critical role in this mitogenic effect.
- The macrophage scavenger receptor (MSR) is implicated in lipoprotein uptake by macrophages.
Purpose of the Study:
- To investigate the specific role of the macrophage scavenger receptor (MSR) in Ox-LDL-induced macrophage growth.
- To determine if MSR mediates the uptake of lyso-PC, contributing to macrophage proliferation.
Main Methods:
- Utilized maleylated bovine serum albumin (maleyl-BSA) as a MSR ligand to inhibit Ox-LDL effects.
- Assessed the competitive inhibition of 125I-Ox-LDL and lyso-PC uptake by MSR.
- Compared Ox-LDL-induced macrophage growth in MSR knockout mice versus wild-type littermates.
Main Results:
- Maleyl-BSA inhibited Ox-LDL-induced macrophage growth and competitively inhibited Ox-LDL and lyso-PC uptake via MSR.
- Maleyl-BSA alone did not induce macrophage growth, even with added lyso-PC.
- Macrophage growth stimulated by Ox-LDL was significantly reduced in MSR knockout mice.
Conclusions:
- The macrophage scavenger receptor (MSR) is crucial for the internalization of lyso-PC from Ox-LDL.
- MSR-mediated lyso-PC uptake is a significant pathway driving Ox-LDL-induced macrophage growth.
- Targeting MSR could offer a strategy to modulate macrophage responses in conditions involving Ox-LDL.