Evidence of macrophage foam cell formation by very low-density lipoproteinreceptor - Interferon-gamma inhibition of very low-density lipoprotein receptor expression and foam cell formation in macrophages

Citation
S. Kosaka et al., Evidence of macrophage foam cell formation by very low-density lipoproteinreceptor - Interferon-gamma inhibition of very low-density lipoprotein receptor expression and foam cell formation in macrophages, CIRCULATION, 103(8), 2001, pp. 1142-1147
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
103
Issue
8
Year of publication
2001
Pages
1142 - 1147
Database
ISI
SICI code
0009-7322(20010227)103:8<1142:EOMFCF>2.0.ZU;2-0
Abstract
Background-Expression of the VLDL receptor, primarily in macrophages, has b een confirmed in human and rabbit atherosclerotic lesions. The high binding affinity of the VLDL receptor for remnant particles implicates the VLDL re ceptor pathway in the foam cell formation mechanism in macrophages, This st udy investigates the effect of interferon (IFN)-gamma on VLDL receptor expr ession in phorbol-12-myristate-13-acetate (PMA)-treated THP-1, HL-60 macrop hages, and human monocyte-derived macrophages, Methods and Results-THP-1 cells were induced to differentiate into macropha ges by PMA treatment. IFN-gamma was added to the medium, and expression of the VLDL receptor was determined, I-125-beta -VLDL degradation study and oi l red O staining were examined. In THP-1 macrophages, VLDL receptor protein expression decreased at 2 days after PMA treatment but increased at 3 days and increased up to 5 days, Scavenger receptor proteins, which were not or iginally present, appeared at 3 days after PMA treatment. IFN-gamma inhibit ed VLDL receptor expression in a dose-and time-dependent manner in macropha ges, However, no inhibitory effect was observed in monocytes, Moreover, IFN -gamma receptor mRNA increased during differentiation to macrophages, I-125 -beta -VLDL degradation study and oil red O staining showed that IFN-gamma significantly inhibited foam cell formation after the uptake of beta -VLDL. LDL receptor-related protein (LRP) and LDL receptor mRNAs were not express ed in macrophages, In PMA-treated HL-60 macrophages and human monocyte-deri ved macrophages, IFN-gamma also inhibited VLDL receptor expression and foam cell formation by beta -VLDL. Conclusions-VLDL receptor expression is upregulated during monocyte-macroph age differentiation. IFN-gamma inhibits VLDL receptor expression and foam c ell formation only in macrophages, Remnant particles induct macrophage foam cell formation through the VLDL receptor pathway.