title: Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration.
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.
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101, United States.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Evanko
authors.forename: Susan
authors.initials: S
authors.lastname: Potter-Perigo
authors.forename: Paul L
authors.initials: PL
authors.lastname: Bollyky
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Nepom
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000166:cytology; D008213:Lymphocyte Activation; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding; D059008:Time-Lapse Imaging / Q000379:methods; D053675:Versicans / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C508322:VCAN protein, human; D053675:Versicans; D006820:Hyaluronic Acid; D003094:Collagen; D006821:Hyaluronoglucosaminidase; D016650:Fluorescein-5-isothiocyanate; D011070:Poly I-C