Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit.
Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group.
Burova
Larissa
L
Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Thern
Anette
A
Pigarevsky
Piter
P
Gladilina
Maria
M
Seliverstova
Valentina
V
Gavrilova
Elena
E
Nagornev
Vladimir
V
Schalén
Claes
C
Totolian
Artem
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D009154:Mutation; D011485:Protein Binding; D011817:Rabbits; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D001426:Bacterial Proteins; D007074:Immunoglobulin G