STREPTOKINASE AS A MEDIATOR OF ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS IN AN EXPERIMENTAL MOUSE MODEL

Group A streptococcal infections are sometimes followed by the inflamm atory kidney disease acute post-streptococcal glomerulonephritis (APSG N). To test the importance of streptokinase in the pathogenesis of thi s disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associat ed ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite fo r the capacity of the strain to induce APSGN in mice. In addition, str eptokinase was demonstrated in the kidneys of mice infected with the n ephritogenic NZ131 and EF514 strains, After infection with the nonneph ritogenic strain S84, neither streptokinase nor C3 deposition were obs erved. Deposition of streptokinase in the glomeruli was detected as so on as 4 days after infection, These findings provide support for the h ypothesis that streptokinase initiates the nephritis process by glomer ular deposition, which leads to local activation of the complement cas cade, Detection of streptokinase in kidney tissue increased with the d egree of glomerular hypercellularity. Thus, the severity of the pathol ogical process may be a reflection of the degree of sterptokinase depo sition.