Beta-migrating very low density lipoproteins induce foam cell formation in mouse mesangial cells.
To elucidate whether beta-migrating very low density lipoproteins (beta-VLDL) induce foam cell formation in mesangial cells or not, surface binding and foam cell formation with beta-VLDL were studied in mouse mesangial cells. Specific binding kinetics for beta-VLDL and low density lipoproteins (LDL) on the mesangial cells were observed with Kd = 3.8 and 13.7 micrograms/ml, and Bmax = 65.9 and 71.9 ng/ml cell protein at 4 degrees C, respectively. The binding of beta-VLDL was inhibited by excess amounts of LDL or beta-VLDL, but not by acetyl-low density lipoproteins. Ligand blotting using beta-VLDL or LDL and immunoblotting using anti-human LDL receptor monoclonal antibody detected the same apparent single protein (approx. 130 kDa). Incorporation of [14C]oleate into cholesteryl ester in mouse mesangial cells was enhanced by beta-VLDL to 3-fold higher than that by LDL, and it was inhibited by chloroquine or anti-human LDL receptor monoclonal antibody. The light microscopic findings also demonstrated that cholesteryl ester deposition increased in these cells incubated with beta-VLDL, but not with LDL. In conclusion, beta-VLDL was specifically taken up by receptor-mediated endocytosis in mouse mesangial cells through LDL receptors, resulting in foam cell formation.
Nishikawa
T
T
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Kobori
S
S
Takeda
H
H
Higashi
T
T
Sato
Y
Y
Sasahara
T
T
Yano
T
T
Kasho
M
M
Anami
Y
Y
Shichiri
M
M
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D015151:Immunoblotting; D008079:Lipoproteins, VLDL / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D011973:Receptors, LDL / Q000378:metabolism*
D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL