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Research article - Peer-reviewed, 2008

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

Liden, Asa; van Wieringen, Tijs; Lannergard, Jonas; Kassner, Anja; Heinegard, Dick; Reed, Rolf K.; Guss, Bengt; Rubin, Kristofer


Fibroblast-mediated collagen gel contraction depends on collagen-binding beta 1 integrins. Perturbation of these integrins reveals an alternative contraction process that is integrin alpha V beta 3-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 alpha V beta 3-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 K-d values of similar to 20 and similar to 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 alpha V beta 3-mediated contraction by C2C12 cells in a concentration-dependent manner having a maximal effect at similar to 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.

Published in

Journal of Biological Chemistry
2008, Volume: 283, number: 3, pages: 1234-1242

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    • UKÄ Subject classification

      Veterinary Science
      Animal and Dairy Science

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