A secreted collagen and fibronectin-binding streptococcal protein modulates cell-mediated collagen gel contraction and interstitial fluid pressure
Research output: Contribution to journal › Article
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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 2008|
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)