Oxidized LDL Increases and Interferon- Decreases Expression of CD36 in Human Monocyte–Derived Macrophages

From the Second Department of Internal Medicine, Osaka University Medical School (T.N., S.N., M.N., J.M.Y., Y.T., A.N., K.M., T.F., K.K.-T., S.Y., Y.M.), and the Department of Blood Transfusion, Osaka University Hospital, Suita (Y.K.), Osaka, Japan.

Correspondence to Shizuya Yamashita, MD, Second Department of Internal Medicine, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka 565, Japan.

Abstract—CD36 is a glycoprotein with an M_r of 88 kDa that is expressed on platelets, monocytes/macrophages, capillary endothelial cells, and adipocytes. We previously demonstrated that CD36 is involved in the uptake of oxidized low density lipoprotein (OxLDL) by using CD36-deficient macrophages (J Clin Invest. 1995;96:1859). However, the regulation of CD36 expression in human monocyte–derived macrophages has not been fully elucidated. The current study attempted to clarify the effect of OxLDL and cytokines, both of which are present in atherosclerotic lesions and may play an important role in atherogenesis, on the expression of CD36. A cell enzyme-linked immunosorbent assay and flow cytometry were used to detect CD36 protein. A ribonuclease protection assay was used to measure CD36 mRNA in human monocyte–derived macrophages. The expression of CD36 was increased during the differentiation of monocytes to macrophages. Incubation of macrophages with 25 µg/mL OxLDL for 24 hours increased the level of CD36 protein by 56% and that of CD36 mRNA by 58%. Lysophosphatidylcholine did not affect the expression of CD36. The effects of OxLDL were demonstrated in macrophages that had already differentiated to the point where CD36 expression was almost maximal. Interferon- (IFN-) reduced the expression of CD36 in a dose-dependent manner. A concentration of 1000 U/mL IFN- significantly reduced the expression of CD36 protein by 57% and that of CD36 mRNA by 30%. In conclusion, CD36 may be important in the formation of foam cells by induction through its ligand (OxLDL). Moreover, some local factors, such as IFN-, may suppress CD36 expression on macrophages in human atherosclerotic lesions.

Key Words: CD36 • oxidized LDL receptor • monocyte-derived macrophages • scavenger receptor • interferon-

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