Adhesion and signaling by B cell-derived exosomes: the role of integrins

FASEB J. 2004 Jun;18(9):977-9. doi: 10.1096/fj.03-1094fje. Epub 2004 Apr 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Calcium / metabolism
  • Calcium Signaling
  • Cations / pharmacology
  • Cell Adhesion* / drug effects
  • Cell Line, Transformed
  • Collagen Type I / metabolism
  • Extracellular Matrix / metabolism
  • Fibroblasts
  • Fibronectins / metabolism
  • Humans
  • Integrin alpha4 / metabolism
  • Integrin beta Chains / metabolism
  • Integrins / metabolism*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Secretory Vesicles / metabolism
  • Secretory Vesicles / physiology*
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cations
  • Collagen Type I
  • Fibronectins
  • Integrin beta Chains
  • Integrins
  • Tumor Necrosis Factor-alpha
  • Integrin alpha4
  • Calcium