CHARACTERIZATION OF CK-BETA-8 AND CK-BETA-8-1 - 2 ALTERNATIVELY SPLICED FORMS OF HUMAN BETA-CHEMOKINE, CHEMOATTRACTANTS FOR NEUTROPHILS, MONOCYTES, AND LYMPHOCYTES, AND POTENT AGONISTS AT CC-CHEMOKINE RECEPTOR-1

Two new members of human beta-chemokine cDNA were isolated based on st ructural and functional similarities to human leukotactin-1. One of th ese clones was identical to the previously isolated human beta-chemoki ne, CK beta 8, whereas the other is a splicing variant of CK beta 8, t herefore named CK beta 8-1. CK beta 8 was short in 51 nucleotides (17 amino acids) compared with CK beta 8-1. The mature proteins of CK beta 8-1 and CK beta 8 consisted of 116 and 99 amino acids with calculated molecular weights of 12,500 and 10,950, respectively. Both CK beta-1 and CK beta 8 were potent agonists at CCR1. These chemokines chemoattr acted neutrophils, monocytes, and lymphocytes, They also significantly suppressed colony formation by human bone marrow, granulocyte-macroph age, erythroid, and multipotential progenitor cells stimulated by comb inations of growth factors. To our knowledge, this is the first exampl e that an alternative splicing produces two active beta-chemokines fro m a single gene. (C) 1998 by The American Society of Hematology.