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Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit

Burova, L; Thern, A; Pigarevsky, P; Gladilina, M; Seliverstova, V; Gavrilova, E; Nagornev, V; Schalén, Claës LU and Totolian, A (2003) In APMIS : acta pathologica, microbiologica, et immunologica Scandinavica1988-01-01+01:00 111(10). p.955-962
Abstract
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... (More)
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 10(9) 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Streptococcus pyogenes, poststreptococcal glomerulonephritis, rabbit, model
in
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica1988-01-01+01:00
volume
111
issue
10
pages
955 - 962
publisher
John Wiley & Sons
external identifiers
  • pmid:14616548
  • wos:000186551400008
  • scopus:0242267010
ISSN
1600-0463
DOI
10.1034/j.1600-0463.2003.1111007.x
language
English
LU publication?
yes
id
5f09e3cf-7504-48d0-a06d-db3d50e30fb4 (old id 295699)
date added to LUP
2007-08-27 12:32:03
date last changed
2018-01-07 06:02:42
@article{5f09e3cf-7504-48d0-a06d-db3d50e30fb4,
  abstract     = {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 10(9) 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.},
  author       = {Burova, L and Thern, A and Pigarevsky, P and Gladilina, M and Seliverstova, V and Gavrilova, E and Nagornev, V and Schalén, Claës and Totolian, A},
  issn         = {1600-0463},
  keyword      = {Streptococcus pyogenes,poststreptococcal glomerulonephritis,rabbit,model},
  language     = {eng},
  number       = {10},
  pages        = {955--962},
  publisher    = {John Wiley & Sons},
  series       = { APMIS : acta pathologica, microbiologica, et immunologica Scandinavica1988-01-01+01:00},
  title        = {Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit},
  url          = {http://dx.doi.org/10.1034/j.1600-0463.2003.1111007.x},
  volume       = {111},
  year         = {2003},
}