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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2020-2026.
Prepublished online as a Blood First Edition Paper on May 25, 2004; DOI 10.1182/blood-2003-12-4157.
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Submitted December 3, 2003
Accepted May 7, 2004
Integrin 4 7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation
Yoshio Katayama, Andres Hidalgo, Anna J Peired, and Paul S Frenette*
Medicine, Mount Sinai School of Medicine, New York, NY, USA; Center for Immunobiology, Mount Sinai School of Medicine, New York, NY, USA
* Corresponding author; email: paul.frenette{at}mssm.edu.
Previous studies have shown that 4 1 (VLA-4) and VCAM-1 play a major role in hematopoietic progenitor cell (HPC) homing to bone marrow (BM). However, the antibody used to block VLA-4 function in the mouse (clone PS/2) is not specific to VLA-4 but inhibits both 4 1 and 4 7 integrins. Here, we have evaluated the contribution of 4 7 in HPC homing to BM. LineagenegSca-1posc-kitpos cells from adult mouse BM and the FDCP-mix progenitor cell line express similar levels of 4 7 by flow cytometry. The 4 7 complex was functional since the chemokine CXCL12 enhanced the adhesion of FDCP-mix to immobilized MAdCAM-1-Fc, and this was completely abrogated by anti- 4 7 (DATK32) or anti- 4 integrins (PS/2). BM intravital microscopy revealed that 4 7 plays a predominant role in initial tethering and rolling but not in firm adhesion of FDCP-mix cells. Using homing assays, we demonstrate that 4 7 on HPCs contributes to about half of all 4 integrin-mediated homing activity. MAdCAM-1 is likely expressed since its inhibition significantly reduced HPC homing. Although there may be other 4 7 integrin ligands involved (e.g. fibronectin and VCAM-1), these data thus suggest that 4 7 and its counterreceptor MAdCAM-1 represent a novel adhesion pathway that significantly contributes to HPC homing to BM.

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