Activation of ephrin A proteins influences hematopoietic stem cell adhesion and trafficking patterns

Ting, Michael J., Day, Bryan W., Spanevello, Mark D. and Boyd, Andrew W. (2010) Activation of ephrin A proteins influences hematopoietic stem cell adhesion and trafficking patterns. Experimental Hematology, 38 11: 1087-1098. doi:10.1016/j.exphem.2010.07.007


Author Ting, Michael J.
Day, Bryan W.
Spanevello, Mark D.
Boyd, Andrew W.
Title Activation of ephrin A proteins influences hematopoietic stem cell adhesion and trafficking patterns
Journal name Experimental Hematology   Check publisher's open access policy
ISSN 0301-472X
1873-2399
0256-9280
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1016/j.exphem.2010.07.007
Volume 38
Issue 11
Start page 1087
End page 1098
Total pages 12
Place of publication Philadelphia Pa., U.S.A.
Publisher Elsevier
Collection year 2011
Language eng
Formatted abstract Objective
To determine if Eph receptors and ephrins can modulate the homing of hematopoietic cells in a murine bone marrow transplantation model.

Materials and Methods
EphA and ephrin A gene expression by mouse hematopoietic stem cells and the progenitor cell line FDCP-1 was determined by real-time reverse transcription polymerase chain reaction and flow cytometry. The effect of ephrin A activation on adhesion of hematopoietic progenitors was determined by in vitro adhesion assays in which cells were exposed to fibronectin or vascular cell adhesion molecule−1 (VCAM-1) and an increasing gradient of immobilized EphA3-Fc. Adhesion to fibronectin and VCAM-1 was further investigated using soluble preclustered EphA3-Fc. We used soluble unclustered EphA3-Fc as an antagonist to block endogenous EphA−ephrin A interactions in vivo. The effect of injecting soluble EphA3-Fc on the mobilization of hematopoietic progenitor cells was examined. We determined the effect on short-term homing by pretreating bone marrow cells with EphA3-Fc or the control IgG before infusion into lethally irradiated mice.

Results
Preclustered and immobilized EphA3-Fc increased adhesion of progenitor cells and FDCP-1 to fibronectin and VCAM-1 (1.6- to 2-fold higher adhesion; p < 0.05) relative to control (0 μ/cm2 EphA3-Fc extracellular molecule alone). Injection of the antagonist soluble EphA3-Fc increased progenitor cell and colony-forming unit−spleen cells in the peripheral blood (42% greater colony-forming unit in culture; p < 0.05, 3.8-fold higher colony-forming unit−spleen) relative to control.

Conclusion

Treating bone marrow cells with EphA3-Fc resulted in a reduction by 31% in donor stem cells homing to the bone marrow and accumulation of donor cells in recipient spleens (50% greater than control) and greater recovery of donor stem cells from the peripheral blood.
Keyword Receptor tyrosine kinase
Bone-marrow
Peripheral-blood
Progenitor cells
EPBH receptors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Sun, 05 Dec 2010, 00:12:47 EST