title: Myocardial tissue damage in rabbits injected with group A streptococci, types M1 and M22. Role of bacterial immunoglobulin G-binding surface proteins.
abstract: Acute rheumatic fever (ARF) and acute poststreptococcal glomerulonephritis (APSGN), two important sequelae of streptococcal throat or skin infections, according to current concepts may be elicited by autoimmune mechanisms due to molecular mimicry between group A streptococci (GAS) and human tissue. In the case of APSGN, however, our experimental data have indicated that GAS immunoglobulin-binding surface proteins (IgG BPs) might be of pathogenic significance by triggering anti-IgG production and immune complex formation leading to renal damage. Thus, rabbits injected with IgG-binding, as opposed to non-binding, GAS strains were found to develop renal deposition of IgG and complement factor C3 and inflammatory and degenerative glomerular changes resembling the picture seen in APSGN. In the present study, cardiac tissue material from rabbits injected with GAS was investigated. After 8 or more weeks of intravenous (i.v.) injections, minimal changes were seen in those animals receiving an IgG non-binding GAS strain, type T27, whereas those animals receiving either of two IgG-binding GAS strains, types M1 or M22, developed strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence of streptococcal IgG-binding activity. Our results demonstrate that myocardial tissue changes may be induced in the rabbit by i.v. injection of whole heat-killed GAS of at least two M serotypes. Conceivably, induction of immune complexes by bacterial IgG BPs may lead to myocardial deposition of IgG, in turn triggering a series of events, involving the complement system and proinflammatory cytokines, with resulting tissue damage. Though many virulence factors may be involved in the development of ARF and APSGN, and a given GAS strain will never cause both, our results may suggest a new pathogenetic mechanism common to these two major non-suppurative complications.
authors.affiliation: Institute of Experimental Medicine, Academy of the Medical Sciences, St. Petersburg, Russia.
authors.forename: L A
authors.initials: LA
authors.lastname: Burova
authors.forename: V A
authors.initials: VA
authors.lastname: Nagornev
authors.forename: P V
authors.initials: PV
authors.lastname: Pigarevsky
authors.forename: M M
authors.initials: MM
authors.lastname: Gladilina
authors.forename: E A
authors.initials: EA
authors.lastname: Gavrilova
authors.forename: V G
authors.initials: VG
authors.lastname: Seliverstova
authors.forename: A A
authors.initials: AA
authors.lastname: Totolian
authors.forename: A
authors.initials: A
authors.lastname: Thern
authors.forename: C
authors.initials: C
authors.lastname: Schalén
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D006321:Heart / Q000382:microbiology*; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009154:Mutation; D009206:Myocardium / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D011817:Rabbits; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G