Adhesion and signaling by B cell-derived exosomes: the role of integrins.
Exosomes are nanometer-sized vesicles secreted by various cells, with potentially diverse roles in physiology. Although emphasis has been placed on their involvement in immune modulation, their potential for more wide-ranging biological effects has not been appreciated. A common exosome feature is the expression of adhesion molecules, which include the integrin family. We have for the first time addressed the possible function of B cell-derived exosome-integrins by examining adhesive interactions of exosomes (immobilized onto beads) with extracellular matrix (ECM) components and cytokine-treated fibroblasts. Integrin (beta1 and beta2) expression was demonstrated by Western blotting and flow cytometry. Binding studies (with blocking antibodies) demonstrated their function in adhesion to collagen-I, fibronectin, and tumor necrosis factor (TNF)-alpha-activated fibroblasts. Exosome adhesion to TNF-alpha-activated fibroblasts also triggered integrin-dependent changes in cytosolic calcium, measured by single cell imaging. Thus, B cell-derived exosomes express functional integrins, which are capable of mediating anchorage to ECM and cell-surface adhesion molecules, and may be a novel mode of delivering adhesion signals at distances beyond that of direct cell-cell contact during inflammation.
Clayton
Aled
A
Section of Clinical Oncology, Department of Medicine, University of Wales College of Medicine, Velindre Hospital, Whitchurch, Cardiff, UK. aled.clayton@velindre-tr.wales.nhs.uk
Turkes
Atilla
A
Dewitt
Sharon
S
Steadman
Robert
R
Mason
Malcolm D
MD
Hallett
Maurice B
MB
D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002412:Cations / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002412:Cations; D024042:Collagen Type I; D005353:Fibronectins; D039641:Integrin beta Chains; D016023:Integrins; D014409:Tumor Necrosis Factor-alpha; D039441:Integrin alpha4; D002118:Calcium