MOLECULAR-CLONING OF A NOVEL HUMAN CC CHEMOKINE LIVER AND ACTIVATION-REGULATED CHEMOKINE (LARC) EXPRESSED IN LIVER - CHEMOTACTIC ACTIVITY FOR LYMPHOCYTES AND GENE LOCALIZATION ON CHROMOSOME

Partial overlapping cDNA sequences likely to encode a novel human CC c hemokine were identified from the GenBank Expressed Sequence Tag data base. Using these sequences, we isolated full-length cDNA encoding a p rotein of 96 amino acid residues with 20-28% identity to other CC chem okines. By Northern blot, this chemokine was mainly expressed in liver among various tissues and strongly induced in several human cell Line s by phorbol myristate acetate. We thus designated this chemokine as L ARC from Liver and Activation-Regulated Chemokine. We mapped the LARC gene close to the chromosomal marker D2S159 at chromosome 2q33-q37 by somatic cell and radiation hybrid mappings and isolated two yeast arti ficial chromosome clones containing the LARC gene from this region. To prepare LARC, we subcloned the cDNA into a baculovirus vector and exp ressed it in insect cells. The secreted protein started at Ala-27 and was significantly chemotactic for lymphocytes. At a concentration of 1 mu g/ml, it also showed a weak chemotactic activity for granulocytes. Unlike other CC chemokines, however, LARC was not chemotactic for mon ocytic THP-I cells or blood monocytes. LARC tagged with secreted alkal ine phosphatase-(His)(6) bound specifically to lymphocytes, the bindin g being competed only by LARC and not by other CC or CXC chemokines. S catchard analysis revealed a single class of receptors for LARC on lym phocytes with a K-d of 0.4 nM and 2100 sites/cell. Collectively, LARC is a novel CC chemokine, which may represent a new group of CC chemoki nes localized on chromosome 2.