Skip to main content
SLU:s publikationsdatabas (SLUpub)

Forskningsartikel2008Vetenskapligt granskadÖppen tillgång

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.

Publicerad i

Journal of Biological Chemistry
2008, Volym: 283, nummer: 3, sidor: 1234-1242