Integrin α4β7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation

Yoshio Katayama, Andrés Hidalgo, Anna Peired, Paul S. Frenette

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Previous studies have shown that α4β1 (very late activation antigen-4 [VLA-4]) and vascular ceil 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 α4β 7 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 roiling 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.

Original languageEnglish (US)
Pages (from-to)2020-2026
Number of pages7
JournalBlood
Volume104
Issue number7
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

Fingerprint

Cell Adhesion Molecules
Bone Marrow Transplantation
Integrins
Integrin alpha4beta1
Hematopoietic Stem Cells
Bone
Bone Marrow
Adhesion
Stem Cells
Hybridomas
Blood Vessels
Clone Cells
Chemokine CXCL12
Cells
Molecules
Fibronectins
Flow cytometry
Flow Cytometry
Assays
Ligands

ASJC Scopus subject areas

  • Hematology

Cite this

Integrin α4β7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation. / Katayama, Yoshio; Hidalgo, Andrés; Peired, Anna; Frenette, Paul S.

In: Blood, Vol. 104, No. 7, 01.10.2004, p. 2020-2026.

Research output: Contribution to journalArticle

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