Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration

Matrix Biol. 2012 Mar;31(2):90-100. doi: 10.1016/j.matbio.2011.10.004. Epub 2011 Nov 20.

Abstract

The ability of lymphocytes to migrate freely through connective tissues is vital to efficient immune function. How the extracellular matrix (ECM) may affect T-cell adhesion and migration is not well understood. We have examined the adhesion and migration of activated human T-lymphocytes on ECM made by fibroblast-like synoviocytes and lung fibroblasts. These cells were minimally interactive until treated with a viral mimetic, Poly I:C. This treatment promoted myofibroblast formation and engendered a higher-order structured ECM, rich in versican and hyaluronan, to which T-cells avidly adhered in a hyaluronidase-sensitive manner. This Poly I:C-induced matrix impeded T-cell spreading and migration on and through synoviocyte monolayers, while hyaluronidase treatment or adding versican antibody during matrix formation reversed the effect on T-cell migration. Hyaluronidase also reversed the spread myofibroblast morphology. These data suggest that the viscous hyaluronan- and versican-rich matrix binds and constrains T-lymphocytes. Using purified matrix components and solid state matrices of defined composition, we uncovered a role for versican in modulating hyaluronan-T-cell interactions. Versican prevented T-cell binding to soluble hyaluronan, as well as the amoeboid shape change on hyaluronan-coated dishes and T-cell penetration of collagen gels. Together, these data suggest that hyaluronan and versican play a role in T-cell trafficking and function in inflamed tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Adhesion
  • Cell Movement*
  • Cells, Cultured
  • Collagen / metabolism
  • Extracellular Matrix / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / metabolism*
  • Hyaluronic Acid / pharmacology
  • Hyaluronoglucosaminidase / metabolism
  • Inflammation / metabolism
  • Lung / cytology
  • Lymphocyte Activation
  • Poly I-C / pharmacology
  • Protein Binding
  • Time-Lapse Imaging / methods
  • Versicans / metabolism*

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • VCAN protein, human
  • Versicans
  • Hyaluronic Acid
  • Collagen
  • Hyaluronoglucosaminidase
  • Fluorescein-5-isothiocyanate
  • Poly I-C