title: Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model.
abstract: Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.
authors.affiliation: Department of Clinical Bacteriology, Umeå University, Sweden. Annika.Nordstrand@climi.umu.se
authors.forename: A
authors.initials: A
authors.lastname: Nordstrand
authors.forename: M
authors.initials: M
authors.lastname: Norgren
authors.forename: J J
authors.initials: JJ
authors.lastname: Ferretti
authors.forename: S E
authors.initials: SE
authors.lastname: Holm
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003171:Complement Pathway, Classical; D005921:Glomerulonephritis / Q000378:metabolism* / Q000382:microbiology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013290:Streptococcal Infections / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000378:metabolism*; D013300:Streptokinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D003176:Complement C3; D007074:Immunoglobulin G; D013300:Streptokinase