Distinct biological effects of macrophage inflammatory protein-1 alpha andstroma-derived factor-1 alpha on CD34(+) hemopoietic cells

Chemokines are important regulators of both hemopoietic progenitor cell (HP C) proliferation and adhesion to extracellular matrix molecules, Here, we c ompared the biological effects of the CC chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) with those of the CXC chemokine stroma-derive d factor-1 alpha (SDF-1 alpha) on immunomagnetically purified CD34(+) cells from leukapheresis products (LP CD34(+)), In particular, studies on chemok ine-induced alterations of LP CD34(+) cell attachment to fibronectin-coated plastic surfaces, proliferation of these cells in colony-forming cell (CFC ) assays and intracellular calcium mobilization were performed, MIP-1 alpha but not SDF-1 alpha was found to increase the adhesion of LP CD34(+) cells to fibronectin in a dose-dependent manner. Both chemokines elicited growth -suppressive effects on LP CD34(+) cells in CFC assays, While MIP-la reduce d the number of granulomonocytic (CFC-GM) and erythroid (BFU-E) colonies to the same extent, SDF-1 alpha showed a significantly greater inhibitory eff ect on CFC-GM than BFU-E, Finally, we demonstrated that SDF-1 alpha but not MIP-1 alpha triggers increases in intracellular calcium in LP CD34(+) cell s. The SDF-1 alpha-induced calcium response was rapid and concentration-dep endent, with a maximal stimulation observed at greater than or equal to 15 ng/ml, In conclusion, our data suggest distinct biological properties of SD F-1 alpha and MIP-1 alpha in terms of modulation of LP CD34(+) cell adhesio n to fibronectin and intracellular calcium levels, However, comparable grow th-suppressive effects on HPC proliferation were observed, indicating that this feature may be independent of chemokine-induced calcium responses.