title: Distinct biological effects of macrophage inflammatory protein-1alpha and stroma-derived factor-1alpha on CD34+ hemopoietic cells.
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-1alpha (MIP-1alpha) with those of the CXC chemokine stroma-derived factor-1alpha (SDF-1alpha) 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-1alpha but not SDF-1alpha 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-1alpha reduced the number of granulomonocytic (CFC-GM) and erythroid (BFU-E) colonies to the same extent, SDF-1alpha showed a significantly greater inhibitory effect on CFC-GM than BFU-E. Finally, we demonstrated that SDF-1alpha but not MIP-1alpha triggers increases in intracellular calcium in LP CD34+ cells. The SDF-1alpha-induced calcium response was rapid and concentration-dependent, with a maximal stimulation observed at > or = 15 ng/ml. In conclusion, our data suggest distinct biological properties of SDF-1alpha and MIP-1alpha 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.
authors: Department of Haematology, University Hospital Essen, Germany.
authors: J
authors: J
authors: Dürig
authors: N G
authors: NG
authors: Testa
authors: C M
authors: CM
authors: Heyworth
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019707:Receptors, Chemokine / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005353:Fibronectins; D019707:Receptors, Chemokine; C080633:macrophage inflammatory protein 1alpha receptor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D002118:Calcium