Evidence that ?7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1.

ABSTRACT: ?4?7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed ?7 integrin. These ?7(+) HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over ?7(-) HSCs. On the other hand, HSCs that lacked ?7 integrin (?7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that ?7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, ?7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the ?4?7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that ?7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.

SUBMITTER: Murakami JL 

PROVIDER: S-EPMC4692116 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature