Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides.
The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 microg/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma.
Engberg
Anna E
AE
School of Pure and Applied Natural Sciences, University of Kalmar, Kalmar 391 82, Sweden.
Sandholm
Kerstin
K
Bexborn
Fredrik
F
Persson
Jenny
J
Nilsson
Bo
B
Lindahl
Gunnar
G
Ekdahl
Kristina N
KN
D000942:Antigens, Bacterial / Q000737:chemistry*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D013499:Surface Properties
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001672:Biocompatible Materials; C055609:C4BPA protein, human; D002352:Carrier Proteins; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens; D010446:Peptide Fragments; C014689:streptococcal M protein