Distinct Biological Effects of Macrophage Inflammatory Protein‐1α and Stroma‐Derived Factor‐1α on CD34+Hemopoietic Cells

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Abstract
Chemokines are important regulators of both hemopoietic progenitor cell (HPC) proliferation and adhesion to extracellular matrix molecules. Here, we compared the biological effects of the CC chemokine macrophage inflammatory protein‐1α (MIP‐1α) with those of the CXC chemokine stroma‐derived factor‐1α (SDF‐1α) on immunomagnetically purified CD34+ cells from leukapheresis products (LP CD34+). In particular, studies on chemokine‐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‐1α but not SDF‐1α 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‐1α reduced the number of granulomonocytic (CFC‐GM) and erythroid (BFU‐E) colonies to the same extent, SDF‐1α showed a significantly greater inhibitory effect on CFC‐GM than BFU‐E. Finally, we demonstrated that SDF‐1α but not MIP‐1α triggers increases in intracellular calcium in LP CD34+ cells. The SDF‐1α‐induced calcium response was rapid and concentration‐dependent, with a maximal stimulation observed at ≥ 15 ng/ml. In conclusion, our data suggest distinct biological properties of SDF‐1α and MIP‐1α in terms of modulation of LP CD34+ cell adhesion to fibronectin and intracellular calcium levels. However, comparable growth‐suppressive effects on HPC proliferation were observed, indicating that this feature may be independent of chemokine‐induced calcium responses.