Distinct biological effects of macrophage inflammatory protein-1alpha and stroma-derived factor-1alpha on CD34+ hemopoietic cells.
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.
Dürig
J
J
Department of Haematology, University Hospital Essen, Germany.
Testa
N G
NG
Heyworth
C M
CM
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
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