Integrin α4β7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation
- 1 October 2004
- journal article
- Published by American Society of Hematology in Blood
- Vol. 104 (7), 2020-2026
- https://doi.org/10.1182/blood-2003-12-4157
Abstract
Previous studies have shown that α4β1 (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 α4β1 and α4β7 integrins. Here we have evaluated the contribution of α4β7 in HPC homing to BM. LineagenegSca-1posc-kitpos cells from adult mouse BM and the factor-dependent cell progenitor (FDCP)—mix progenitor cell line express similar levels of α4β7 by flow cytometry. The α4β7 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-α4β7 (hybridoma clone DATK32) or anti-α4 integrins (PS/2). BM intravital microscopy revealed that α4β7 plays a predominant role in initial tethering and rolling but not in firm adhesion of FDCP-mix cells. Using homing assays, we demonstrate that α4β7 on HPCs contributes to about half of all α4 integrin–mediated homing activity following BM transplantation. MAdCAM-1 is likely expressed since its inhibition significantly reduced HPC homing. Although there may be other α4β7 integrin ligands involved (eg, fibronectin and VCAM-1), these data thus suggest that α4β7 and its counterreceptor MAdCAM-1 represent a novel adhesion pathway mediating HPC homing to BM.Keywords
This publication has 41 references indexed in Scilit:
- IntegrinsCell, 2002
- Effect of Divalent Cations on the Affinity and Selectivity of α4 Integrins Towards the Integrin Ligands Vascular Cell Adhesion Molecule-1 and Mucosal Addressin Cell Adhesion Molecule-1: Ca 2+ Activation of Integrin α4β1 Confers a Distinct Ligand SpecificityCell Communication & Adhesion, 2002
- Molecular pathways in bone marrow homing: dominant role of α4β1 over β2-integrins and selectinsBlood, 2001
- MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease)Hepatology, 2001
- Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule‐1, given early in the course of disease progressionImmunology & Cell Biology, 2000
- The role of CS1 moiety of fibronectin in VLA4‐mediated haemopoietic progenitor traffickingBritish Journal of Haematology, 1997
- The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral BloodThe Journal of Experimental Medicine, 1997
- Critical role for β7 integrins in formation of the gut-associated lymphoid tissueNature, 1996
- An Alternately Spliced mRNA Encoding Functional Domains of Murine MAdCAM-1Biochemical and Biophysical Research Communications, 1995
- Identification of a murine Peyer's patch—specific lymphocyte homing receptor as an integrin molecule with an α chain homologous to human VLA-4αCell, 1989