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Volume 272, Number 27, Issue of July 4, 1997 pp. 16778-16782
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Cloning and Characterization of HB₂, a Candidate High Density Lipoprotein Receptor
SEQUENCE HOMOLOGY WITH MEMBERS OF THE IMMUNOGLOBULIN SUPERFAMILY OF MEMBRANE PROTEINS

(Received for publication, April 16, 1997)

Akiyo Matsumoto , Alana Mitchell ^§ , Hideaki Kurata , Louise Pyle ^§ , Kazuo Kondo , Hiroshige Itakura and Noel Fidge ^§

From the ^§ Baker Medical Research Institute, Melbourne, Victoria 3181, Australia and the  National Institute of Health and Nutrition, Tokyo 162, Japan

The protection against coronary artery disease attributed to high density lipoprotein (HDL) may be associated with several functions, including its central role in reverse cholesterol transport, possible antioxidant and antithrombotic properties and others not yet identified which may depend on specific interactions between HDL and cell receptors. Several HDL-binding proteins have been identified including two candidate liver HDL receptors, HB₁ and HB₂ recently purified in this laboratory. We now report the cloning, sequencing, and some properties of HB₂, the most abundant of the pair. It shows significant homology with the adhesion molecules ALCAM and BEN of the immunoglobulin superfamily and the cDNA, when transfected into HepG2 or COS cells, caused specific HDL₃ binding to increase by 80-100%. Further, ligand blotting of glycoproteins isolated from phorbol 12-myristate 13-acetate-treated THP-1 cells or from transfected HepG2 and Chinese hamster ovary cells also provided evidence of increased binding of HDL₃ to HB₂. Differentiation of THP-1 cells into macrophages resulted in a striking increase in HB₂ mRNA which was attenuated if cells were cholesterol-loaded by incubation with acetylated low density lipoprotein. If the interaction between HDL and HB₂ reduces the adhesion-induced inflammatory cellular events that characterize arterial wall injury, thereby achieving the protection associated with higher plasma levels of HDL, these findings may provide a clue to one mitigating effect of HDL in heart disease.

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