Distinct roles of integrins α6 and α4 in homing of fetal liver hematopoietic stem and progenitor cells

Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha 6 and alpha A integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hernatopoietic progenitor cells (HPCs) to adult BM by using integrin alpha 6 gene-deleted mice and functionblocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca1 (+)Kit(+) (LSK) cells. Deletion of integrin alpha 6 receptor or inhibition by a functionblocking antibody inhibited FL LSK cell adhesion to its extracellular ligands, laminins-411 and -511 in vitro, and significantly reduced homing of HPCs to BM. In contrast, the anti-integrin alpha 6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin alpha 6 gene-deleted FL HSCs did not display any homing or engraftment defect compared with wildtype littermates. In contrast, inhibition of integrin alpha 4 receptor by a functionblocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin alpha 6 and alpha 4 receptors during homing of fetal HSCs and HPCs.