Characterization of CKβ8 and CKβ8-1:: Two alternatively spliced forms of human β-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 structural and functional similarities to human leukotactin-1. One of these clones was identical to the previously isolated human beta-chemokine, CK beta 8, whereas the other is a splicing variant of CK beta 8, therefore 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 chemoattracted neutrophils, monocytes, and lymphocytes, They also significantly suppressed colony formation by human bone marrow, granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. To our knowledge, this is the first example that an alternative splicing produces two active beta-chemokines from a single gene. (C) 1998 by The American Society of Hematology.