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 Blood, 1 May 2006, Vol. 107, No. 9, pp. 3503-3510.
Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-10-3932.

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Submitted October 3, 2005
Accepted December 20, 2005

Contribution of {alpha}6-integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with {alpha}4-integrins

Hong Qian, Karl Tryggvason, Sten E Jacobsen, and Marja Ekblom*

Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

* Corresponding author; email: marja.ekblom{at}med.lu.se.

The laminin receptor integrin {alpha}6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. We have studied its role for homing of stem and progenitor cells to mouse hematopoietic tissues in vivo. A function-blocking anti-integrin {alpha}6 antibody significantly reduced progenitor cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding retention of progenitors in blood. Remarkably, the anti-integrin {alpha}6 antibody profoundly inhibited BM homing of long-term multilineage engrafting stem cells, studied by competitive repopulation assay and analysis of donor derived lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar profound inhibition of long-term stem cell homing was obtained by using a function-blocking antibody against {alpha}4 integrin, studied in parallel. Furthermore, the anti-integrin {alpha}6 and {alpha}4 antibodies synergistically inhibited homing of short-term repopulating stem cells. Intravenous injection of anti-integrin {alpha}6 antibodies, in contrast to antibodies against {alpha}4 integrin, did not mobilize progenitors or enhance cytokine-induced mobilization by G-CSF. Our results provide the first evidence for a distinct functional role of integrin {alpha}6 receptor during hematopoietic stem and progenitor cell homing and collaboration of {alpha}6 integrin with {alpha}4 integrin receptors during homing of short-term stem cells.


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