A secreted collagen and fibronectin-binding streptococcal protein modulates cell-mediated collagen gel contraction and interstitial fluid pressure

Research output: Contribution to journalArticle

Abstract

Fibroblast-mediated collagen gel contraction depends on collagen-binding ss1 integrins. Perturbation of these integrins reveals an alternative contraction process that is integrin aVss3-dependent and platelet-derived growth factor (PDGF) BB-stimulated. Connective tissue cells actively control interstitial fluid pressure (IFP) and inflammation-induced lowering of IFP provides a driving force for edema formation. PDGF-BB normalizes a lowered IFP by an aVss3-dependent process. A potential modulation of IFP by extracellular matrix-binding bacterial proteins has previously not been addressed. The fibronectin (FN) -binding protein FNE is specifically secreted by the highly virulent Streptococcus equi subspecies equi. FNE bound FN and native collagen type I with Kd:s of ~20 and ~50 nM determined by solid-phase binding assays. Rotary shadowing revealed a single FNE-binding site located at on average 122 nm from the C-terminus of procollagen type I. FNE induced aVss3-mediated contraction by C2C12 cells in a concentration-dependent manner having a maximal effect at ~100 nM. This activity of FNE required cellular FN, and FNE acted synergistically to added plasma FN or PDGF-BB. FNE enhanced binding of soluble FN to immobilized collagen, and conversely the binding of collagen to immobilized FN. Marked bell-shaped concentration dependences for these interactions suggest that FNE forms a bridge between FN and collagen. Finally, FNE normalized dermal IFP lowered by anaphylaxis. Our data suggest that secreted FNE normalized lowering of IFP by stimulating connective tissue cell contraction.

Details

Authors
  • Åsa Liden
  • Tijs van Wieringen
  • Jonas Lannergard
  • Anja Kassner
  • Dick Heinegård
  • Rolf K Reed
  • Bengt Guss
  • Kristofer Rubin
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity
Original languageEnglish
Pages (from-to)1234-1242
JournalJournal of Biological Chemistry
Volume283
Issue number3
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)