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(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

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