Heparin-inhibitable basement membrane-binding protein of Streptococcus pyogenes

Solubilized surface proteins of Streptococcus pyogenes serotype M6 were found by indirect immunofluorescence assays to bind selectively to proteoglycan-containing regions of basement membranes of kidney and cardiac muscle in vitro. Epithelial, endothelial, and interstitial cells were unstained. Binding of streptococcal protein to basement membranes was competitively inhibited by heparin and, to a lesser extent, by heparan sulfate. Weak inhibition was also observed with other glycosaminoglycans, including dermatan sulfate, chondroitin sulfate, and hyaluronic acid. Type IV collagen, gelatin, serum fibronectin, glucuronic acid, and a selection of monosaccharides had no significant effects on binding. The heparin-inhibitable basement membrane-binding protein was purified by affinity chromatography on heparin-Sepharose 6-B. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and urea dissociated the affinity-purified protein into two polypeptides of 9,000 and 15,000 mrs. Chemical analyses revealed that the purified protein was devoid of cysteine, amino and neutral sugars, and phosphate. Thus, the polypeptides are not glycosylated or complexed with trace amounts of lipoteichoic acid or polysaccharide. Binding of purified protein to tissue was determined by direct radioassay and indirect immunofluorescence and was inhibitable by heparin. Although the in vivo effects of this streptococcal component remain to be determined, its deposition on basement membranes in vitro supports the hypothesis that it contributes to the pathogenesis of poststreptococcal glomerulonephritis or acute rheumatic fever.