| First Author | Katayama Y | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 7 | Pages | 2020-6 |
| PubMed ID | 15161666 | Mgi Jnum | J:93764 |
| Mgi Id | MGI:3505660 | Doi | 10.1182/blood-2003-12-4157 |
| Citation | Katayama Y, et al. (2004) Integrin alpha4beta7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation. Blood 104(7):2020-6 |
| abstractText | Previous studies have shown that alpha4beta1 (very late activation antigen-4 [VLA-4]) and vascular cell adhesion molecule-1 (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 (hybridoma clone PS/2) is not specific to VLA-4 but inhibits both alpha4beta1 and alpha4beta7 integrins. Here we have evaluated the contribution of alpha4beta7 in HPC homing to BM. Lineage(neg)Sca-1(pos)c-kit(pos) cells from adult mouse BM and the factor-dependent cell progenitor (FDCP)-mix progenitor cell line express similar levels of alpha4beta7 by flow cytometry. The alpha4beta7 complex was functional since the chemokine CXCL12 enhanced the adhesion of FDCP-mix to immobilized mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and this was completely abrogated by anti-alpha4beta7 (hybridoma clone DATK32) or anti-alpha4 integrins (PS/2). BM intravital microscopy revealed that alpha4beta7 plays a predominant role in initial tethering and rolling but not in firm adhesion of FDCP-mix cells. Using homing assays, we demonstrate that alpha4beta7 on HPCs contributes to about half of all alpha4 integrin-mediated homing activity following BM transplantation. MAdCAM-1 is likely expressed since its inhibition significantly reduced HPC homing. Although there may be other alpha4beta7 integrin ligands involved (eg, fibronectin and VCAM-1), these data thus suggest that alpha4beta7 and its counterreceptor MAdCAM-1 represent a novel adhesion pathway mediating HPC homing to BM. |
