title: Tetraspanins CD81 and CD82 facilitate α4β1-mediated adhesion of human erythroblasts to vascular cell adhesion molecule-1.
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, 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 α4β1 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.
authors.affiliation: Bristol Institute for Transfusion Sciences, Bristol, United Kingdom. frances.spring@nhsbt.nhs.uk
authors.forename: Frances A
authors.initials: FA
authors.lastname: Spring
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Griffiths
authors.forename: Tosti J
authors.initials: TJ
authors.lastname: Mankelow
authors.forename: Christopher
authors.initials: C
authors.lastname: Agnew
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Parsons
authors.forename: Joel A
authors.initials: JA
authors.lastname: Chasis
authors.forename: David J
authors.initials: DJ
authors.lastname: Anstee
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001491:Basophils / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D051861:Kangai-1 Protein / Q000378:metabolism*; D008024:Ligands; D018613:Microscopy, Confocal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D060185:Tetraspanin 24 / Q000378:metabolism; D060225:Tetraspanin 28 / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000906:Antibodies; C554715:CD151 protein, human; C554798:CD81 protein, human; C497688:CD82 protein, human; D000939:Epitopes; D005353:Fibronectins; D039041:Integrin alpha4beta1; D051861:Kangai-1 Protein; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D060185:Tetraspanin 24; D060225:Tetraspanin 28; D019010:Vascular Cell Adhesion Molecule-1