Tetraspanins CD81 and CD82 Facilitate alpha 4 beta 1-Mediated Adhesion of Human Erythroblasts to Vascular Cell Adhesion Molecule-1

Frances A. Spring*, Rebecca E. Griffiths, Tosti J. Mankelow, Christopher Agnew, Stephen F. Parsons, Joel A. Chasis, David J. Anstee

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)

Abstract

The proliferation and terminal differentiation of erythroid progenitors occurs in human bone marrow within erythroblastic islands, specialised structures consisting of a central macrophage surrounded by developing erythroid cells. Many cell-cell and cell-matrix adhesive interactions maintain and regulate the co-ordinated daily production of reticulocytes. Erythroid cells express only one integrin, alpha 4 beta 1, throughout differentiation, and its interactions with both macrophage Vascular Cell Adhesion Molecule-1 and with extracellular matrix fibronectin are critical for erythropoiesis. We observed that proerythroblasts expressed a broad tetraspanin phenotype, and investigated whether any tetraspanin could modulate integrin function. A specific association between alpha 4 beta 1 and CD81, CD82 and CD151 was demonstrated by confocal microscopy and co-immune precipitation. We observed that antibodies to CD81 and CD82 augmented adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 but not to the fibronectin spliceoforms FnIII(12-IIICS-15) and FnIII(12-15). In contrast, different anti-CD151 antibodies augmented or inhibited adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 and the fibronectin spliceoform FnIII(12-IIICS-15) but not to FnIII12-15. These results strongly suggest that tetraspanins have a functional role in terminal erythropoiesis by modulating interactions of erythroblast a4b1 with both macrophages and extracellular matrix.

Original languageEnglish
Article number62654
Number of pages15
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 21 May 2013

Keywords

  • STROMAL MACROPHAGES
  • HUMAN BONE-MARROW
  • FIBRONECTIN
  • ALPHA-4 INTEGRINS
  • BLOOD-GROUP ANTIGENS
  • ERYTHROID-DIFFERENTIATION
  • IN-VIVO
  • LATE ACTIVATION ANTIGEN-4
  • HEMATOPOIETIC PROGENITORS
  • INTEGRIN ALPHA(4)BETA(1)

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