Differentiation of CD34+ cells from human cord blood and murine bone marrow is suppressed by C6 beta-chemokines.

Several recently identified chemokines, Lkn-1, CKbeta8-1, MRP-2, and Mu C10 (MRP-1), are classified as C6 beta-chemokines. All of these chemokines have been found to suppress colony formation by bone marrow (BM) myeloid progenitors. Since cord blood (CB), like BM, contains CD34-positive cells, we examined the effects of these chemokines on CD34+ cells isolated from human CB. Lkn-1 and CKbeta8-1 suppressed colony formation by multi-potential granulocyte erythroid mega-karyocyte macrophages (CFU-GEMM), granulocyte-macrophages (CFU-GM), and erythroid (BFU-E) cells among the CD34+ cells from CB. CC chemokine receptor 1 (CCR1) that is known to be a receptor for Lkn-1 and CKbeta8-1 in neutrophils, monocytes, and lymphocytes, was also present on the surface of CD34+ cells from CB. Taken together these results suggest that Lkn-1 and CKbeta8-1 are active in inhibiting myeloid progenitor cells from both BM and CB. Macrophage inflammatory protein related protein-2 (mMRP-2) and Mu C10 (mMRP-1), which are murine C6 beta-chemokines, also inhibited colony formation by CB CD34+ cells. The inhibitory activity of these chemokines suggests that they may protect hematopoietic progenitors from the cytotoxic effects of the antiblastic drugs used in cancer therapy.