Foam cell formation but not oxLDL cytotoxicity is inhibited by CD36 down regulation by the macrophage antioxidant 7,8-dihydroneopterin

• Published in: The international journal of biochemistry & cell biology 2021-04, Vol.133, p.105918-105918, Article 105918
• Main Authors: Ghodsian, Nooshin, Yeandle, Anthony, Gieseg, Steven P.
• Format: Article
• Language: English
• Subjects: CD36; Foam cell; Macrophage; Neopterin; Oxidised low-density lipoprotein; Regulation
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2021.105918

Cluster of differentiation 36 (CD36) is a key scavenger receptor in the control of macrophage uptake of oxidised low-density lipoproteins (oxLDL). CD36 expression levels are not down regulated by intracellular cholesterol but are upregulated by oxidised low density lipoprotein (oxLDL) leading to the formation of lipid loaded foam cells, a major constituent of atherosclerotic plaques. We have previous shown that CD36 is down regulated by 7,8-dihydroneopterin, an antioxidant generated by γ-interferon activated macrophages. How CD36 down regulation affects oxLDL induced cytotoxicity, CD36 oxLDL upregulation and foam cell formation is examined using human monocyte like U937 cell line as a model system of human macrophages. Low density lipoprotein (LDL) was prepared by ultracentrifugation from human plasma and oxidised in copper chloride. CD36 levels in U937 cells were measured by western blot analysis. and lipid accumulation was measured by oil red-O staining and 7-ketocholesterol accumulation by high performance liquid chromatography. Cell viability was measured by flow cytometry analysis after propidium iodide staining. 7,8-dihydroneopterin concentrations above 100 μM caused a concentration and time dependent decrease in cellular CD36 levels to 20 % of the untreated cells after 24 h. Upregulation of CD36 by oxLDL was inhibited by 7,8-dihydroneopterin treatment. The CD36 down regulation was associated with decrease in foam cell formation but not a reduction on oxLDL cytotoxicity. 7,8-dihydroneopterin down regulated CD36 in U937 cells, inhibiting foam cell formation but not oxLDL mediated cell death. 7,8-dihydroneopterin may modulate foam cell formation in atherosclerotic plaques.