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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:106-114.)
© 1996 American Heart Association, Inc.

Articles

Decrease in Scavenger Receptor Expression in Human Monocyte–Derived Macrophages Treated With Granulocyte Macrophage Colony-Stimulating Factor

Maaike A. van der Kooij; Olivier H. Morand; Herman J. Kempen; Theo J.C. van Berkel

From the Pharma Division (M.A. van der K., O.H.M., H.J.K.), Preclinical Research, F Hoffmann–La Roche Ltd, Basel, Switzerland, and the Division of Biopharmaceutics (M.A. van der K., T.J.C. van B.), Leiden/Amsterdam Center for Drug Research, University of Leiden, Leiden, Netherlands.

Correspondence to Maaike A. van der Kooij, Pharma Division, Preclinical Research, PRPV, B68/340, F Hoffmann–La Roche Ltd, CH-4002 Basel, Switzerland.

Abstract To determine whether scavenger receptors are susceptible to regulation by granulocyte macrophage colony-stimulating factor (GM-CSF), a macrophage-specific cytokine, human monocytes were differentiated into macrophages in the absence or presence of 20 U/mL GM-CSF. Binding, uptake, and degradation of acetylated LDL (Ac-LDL) and oxidized LDL (Ox-LDL) were measured. Treatment with GM-CSF resulted in a significant twofold to threefold decrease in the number of binding sites for Ac-LDL and Ox-LDL on the surface of macrophages without affecting the affinity of the receptor for these ligands. Competition experiments revealed that two binding sites were responsible for the recognition and uptake of Ac-LDL: one specific for Ac-LDL and one that recognized both Ac-LDL and Ox-LDL. No binding site specific for Ox-LDL could be detected in either control or GM-CSF–treated macrophages. Treatment of human monocyte–derived macrophages with GM-CSF resulted in a decrease of the Ac-LDL/Ox-LDL receptor but did not affect the binding site specific for Ac-LDL. Northern blot analysis showed that mRNA levels of both types I and II scavenger receptor were reduced in macrophages differentiated in the presence of GM-CSF. Human macrophages that were differentiated in the presence of GM-CSF accumulated 50% fewer cholesteryl esters. Taken together, these results indicate that GM-CSF can downregulate both types I and II scavenger receptor in human monocyte–derived macrophages, which might have implications for foam cell formation.

Key Words: granulocyte macrophage colony-stimulating factor • atherosclerosis • macrophage • scavenger receptor • cholesterol

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