This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van der Kooij, M. A. Articles by Morand, O. H. Search for Related Content PubMed PubMed Citation Articles by van der Kooij, M. A. Articles by Morand, O. H.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3107-3116.)
© 1997 American Heart Association, Inc.

Articles

Human Monocyte–Derived Macrophages Express an 120-kD Ox-LDL Binding Protein With Strong Identity to CD68

Maaike A. van der Kooij; Elisabeth M. von der Mark; J. Kar Kruijt; Agnes van Velzen; Theo J.C. van Berkel; ; Olivier H. Morand

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

Correspondence to Dr O.H. Morand, c/o Hoffmann–La Roche Ltd, Pharma Division, Preclinical Research, PRPV, B68/R334, Grenzacherstrasse 124, CH-4070 Basel, Switzerland. E-mail olivier.morand{at}roche.com

Abstract A protein that specifically binds oxidized LDL (Ox-LDL) has recently been characterized in mouse peritoneal macrophages and identified as macrosialin, a protein with a molecular weight of 95 kD. First, the present work shows that human monocyte–derived macrophages express a membrane protein with a molecular weight of 120 kD that selectively binds Ox-LDL. Second, we tested whether this 120-kD Ox-LDL binding protein had any relation to CD68, the human homologue of macrosialin. The following evidence was obtained to support the role of CD68 as an Ox-LDL binding protein: (1) Ligand blots with Ox-LDL and Western blots with Ki-M6, an anti–human CD68 monoclonal antibody, revealed a single band with a molecular weight of 120 kD under reducing and nonreducing condition. (2) The expression patterns of the 120-kD Ox-LDL binding membrane protein and of CD68 paralleled each other during monocyte/macrophage differentiation. (3) Digestion with N-glycosidase F demonstrated that both CD68 and the Ox-LDL binding protein are glycoproteins; both showed a similar shift of 18 kD in apparent molecular weight. (4) CD68, probed with monoclonal antibody Ki-M6, and the 120-kD Ox-LDL binding protein were coprecipitated with EBM11, another anti-CD68 antibody. About 5000 molecules of CD68 are expressed on the cell surface of human macrophages. Ligation of ¹²⁵I–Ki-M6 to cells leads to its internalization and degradation. This capacity would be sufficient to allow for the specific uptake and degradation of Ox-LDL. Taken together, these data support a role for CD68 as a specific Ox-LDL binding protein in human monocyte–derived macrophages.

Key Words: atherosclerosis • macrophages • oxidized LDL • CD68

This article has been cited by other articles:

				M. C. de Beer, Z. Zhao, N. R. Webb, D. R. van der Westhuyzen, and W. J. S. de Villiers Lack of a direct role for macrosialin in oxidized LDL metabolism J. Lipid Res., April 1, 2003; 44(4): 674 - 685. [Abstract] [Full Text] [PDF]

				T. Mäkitie, P. Summanen, A. Tarkkanen, and T. Kivelä Tumor-Infiltrating Macrophages (CD68+ Cells) and Prognosis in Malignant Uveal Melanoma Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1414 - 1421. [Abstract] [Full Text]

				V. Terpstra, E. S. van Amersfoort, A. G. van Velzen, J. Kuiper, and T. J. C. van Berkel Hepatic and Extrahepatic Scavenger Receptors : Function in Relation to Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1860 - 1872. [Full Text] [PDF]

				G. Chinetti, F. G. Gbaguidi, S. Griglio, Z. Mallat, M. Antonucci, P. Poulain, J. Chapman, J.-C. Fruchart, A. Tedgui, J. Najib-Fruchart, et al. CLA-1/SR-BI Is Expressed in Atherosclerotic Lesion Macrophages and Regulated by Activators of Peroxisome Proliferator-Activated Receptors Circulation, May 23, 2000; 101(20): 2411 - 2417. [Abstract] [Full Text] [PDF]

				M Kostich, A Fire, and D. Fambrough Identification and molecular-genetic characterization of a LAMP/CD68-like protein from Caenorhabditis elegans J. Cell Sci., January 7, 2000; 113(14): 2595 - 2606. [Abstract] [PDF]

				N. Hrboticky, G. Draude, G. Hapfelmeier, R. Lorenz, and P. C. Weber Lovastatin Decreases the Receptor-Mediated Degradation of Acetylated and Oxidized LDLs in Human Blood Monocytes During the Early Stage of Differentiation Into Macrophages Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1267 - 1275. [Abstract] [Full Text] [PDF]