CLONING AND CHARACTERIZATION OF HB2, A CANDIDATE HIGH-DENSITY-LIPOPROTEIN RECEPTOR - SEQUENCE HOMOLOGY WITH MEMBERS OF THE IMMUNOGLOBULIN SUPERFAMILY OF MEMBRANE-PROTEINS

The protection against coronary artery disease attributed to high dens ity lipoprotein (HDL) may be associated with several functions, includ ing its central role in reverse cholesterol transport, possible antiox idant and antithrombotic properties and others not yet identified whic h may depend on specific interactions between HDL and cell receptors. Several HDL-binding proteins have been identified including two candid ate liver HDL receptors, HB1 and HB2 recently purified in this laborat ory, 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 an d the cDNA, when transfected into HepG2 or eos cells, caused specific HDL3 binding to increase by 80-100%. Further, ligand blotting of glyco proteins isolated from phorbol 12-myristate 13-acetate-treated THP-1 c ells or from transfected HepG2 and Chinese hamster ovary cells also pr ovided evidence of increased binding of HDL3 to HB2, Differentiation o f THP-1 cells into macrophages resulted in a striking increase in HB2 mRNA which was attenuated if cells were cholesterol-loaded by incubati on with attenuated law density lipoprotein. If the interaction between HDL and NE, reduces the adhesion-induced inflammatory cellular events that characterize arterial wall injury, thereby achieving the protect -ion associated with higher plasma levels of HDL, these findings may p rovide a clue to one mitigating effect of HDL in heart disease.