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Tetraspanins CD81 and CD82 Facilitate α4β1-Mediated Adhesion of Human Erythroblasts to Vascular Cell Adhesion Molecule-1

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [3];  [2];  [4];  [2]
  1. Bristol Institute for Transfusion Sciences, Bristol (United Kingdom); DOE/OSTI
  2. Bristol Institute for Transfusion Sciences, Bristol (United Kingdom)
  3. Bristol University (United Kingdom)
  4. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

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, α4β1, 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 α4βb1 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 FnIII12-IIICS-15 and FnIII12–15. In contrast, different anti-CD151 antibodies augmented or inhibited adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 and the fibronectin spliceoform FnIII12-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 α4β1 with both macrophages and extracellular matrix.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute for Health Research; Department of Health (England); Biological and Biotechnology Research Council; National Institutes of Health (NIH)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627607
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 5 Vol. 8; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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