Submitted May 12, 2006
Accepted October 23, 2006
Endolyn (CD164) Modulates the CXCL12-Mediated Migration
of Umbilical Cord Blood CD133+ Cells
Sinead P Forde, Britt Jorgensen Tye, Sarah E Newey, Maria Roubelakis, Jon Smythe, Colin P McGuckin, Ruth Pettengell, and Suzanne M Watt*
Stem Cell Laboratory, National Blood Service, National Blood & Transplant Authority, Oxford, United Kingdom
Nuffield Dept of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom
Haematological Sciences & the International Centre for Life, University of Newcastle upon Tyne, Newcastle, United Kingdom
St George's, University of London, United Kingdom
* Corresponding author; email: suzanne.watt{at}nbs.nhs.uk.
Hematopoietic stem/progenitor cell (HSC/HPC) homing to specific microenvironmental niches involve interactions between multiple receptor-ligand pairs. Although CXCL12/CXCR4 play a central role in these events, CXCR4 regulators that provide the specificity for such cells to lodge and be retained in particular niches are poorly defined. Here, we provide evidence that the sialomucin, endolyn (CD164), an adhesion receptor that regulates CD34+ cell adhesion to bone marrow stroma and recruitment of CD34+CD38lo/- cells into cycle, associates with CXCR4. The class II 103B2 monoclonal antibody which binds the CD164 N-linked glycan-dependent epitope or CD164 knockdown by RNA interference significantly inhibits the migration of CD133+ HPC towards CXCL12 in vitro. On presentation of CXCL12 on fibronectin, CD164 associates with CXCR4, an interaction that temporally follows the association of CXCR4 with the integrins, VLA-4 and VLA-5. This coincides with signaling through the CXCR4 receptor via PKC-
and Akt, which were disrupted on loss of CD164, while MAPK signaling was unaffected. We therefore demonstrate a novel association between three distinct families of cell surface receptors that regulate cell migratory responses and identify a new role for CD164. We propose that this lends specificity to the homing and lodgement of these cells within the bone marrow niche.
