MOLECULAR-CLONING OF LEUKOTACTIN-1 - A NOVEL HUMAN BETA-CHEMOKINE, A CHEMOATTRACTANT FOR NEUTROPHILS, MONOCYTES, AND LYMPHOCYTES, AND A POTENT AGONIST AT CC-CHEMOKINE RECEPTOR-1 AND RECEPTOR-3

A new member of human beta-chemokine cDNA was isolated and named leuko tactin-1 (Lkn-1). Lkn-1, along with murine macrophage inflammatory pro tein-related protein-1 and -2, defines a subgroup of beta-chemokines b ased on two conserved cysteines in addition to the four others conserv ed in all beta-chemokines. The putative mature Lkn-1 is composed of 92 amino acids with a calculated m.w. of 10,162. The Lkn-1 gene was mapp ed to human chromosome 17, region q12. Recombinant Lkn-1 was a potent chemoattractant for neutrophils, monocytes, and lymphocytes and induce d calcium flux in these cells, Lkn-1 specifically induced calcium flux in CCR1- and CCR3-expressing HOS cell lines. Lkn-1 suppressed colony formation by human granulocyte-macrophage, erythroid, and multipotenti al progenitor cells stimulated by combinations of growth factors. Henc e, we have isolated and characterized a human C6 beta-chemokine that i s a potent agonist at CCR1 and CCR3 and shows broad biologic activitie s, including leukocyte chemoattraction.