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and Stroma-Derived Factor-1
on CD34+ Hemopoietic Cells
a Department of Haematology, University Hospital Essen, Essen, Germany;
b CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom
Key Words. Chemokines • MIP-1
• SDF-1
• Hemopoietic
cells • Calcium flux • Growth
inhibition • Adhesion
Dr. Clare Heyworth, CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom.
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-1
(MIP-1
) with those of the CXC chemokine stroma-derived
factor-1
(SDF-1
) 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-1
but not SDF-1
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-1
reduced the number of granulomonocytic
(CFC-GM) and erythroid (BFU-E) colonies to the same extent, SDF-1
showed a significantly greater inhibitory effect on CFC-GM than
BFU-E. Finally, we demonstrated that SDF-1
but not MIP-1
triggers increases in intracellular calcium in LP CD34+
cells. The SDF-1
-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-1
and MIP-1
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.
This article has been cited by other articles:
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J.-J. Lataillade, D. Clay, C. Dupuy, S. Rigal, C. Jasmin, P. Bourin, and M.-C. L. Bousse-Kerdiles Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival Blood, February 1, 2000; 95(3): 756 - 768. [Abstract] [Full Text] [PDF] |
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