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Streptococcal pyrogenic exotoxin A and streptolysin O enhance polymorphonuclear leukocyte binding to gelatin matrixes
A E Bryant1, M A Kehoe, D L Stevens
1VA Medical Center, Infectious Diseases Section, Boise, Idaho 83702.
Abstract:
Autopsy data from cases of streptococcal toxic shock demonstrate accumulation of polymorphonuclear leukocytes (PMNL) within lung and soft tissue microvasculature. Because of the increased prevalence of streptococcal pyrogenic exotoxin A (SPEA)-producing strains associated with streptococcal toxic shock syndrome, experiments were done to determine whether SPEA or streptolysin O (SLO, a thiol-activated cytolysin produced by all group A streptococci) could stimulate PMNL-dependent adherence mechanisms in vitro. SPEA (0.01-10 micrograms/5.5 x 10(6) PMNL) only modestly enhanced PMNL adherence over the entire range of concentrations tested. In contrast, SLO-induced PMNL binding was highly dose dependent (maximal binding, 55.1 +/- 1.6% at 0.5 hemolytic units/5.5 x 10(6) PMNL) and was mediated by CD11/CD18 adherence glycoprotein.
Insights
Streptolysin O (SLO) significantly enhances polymorphonuclear leukocyte (PMNL) adherence in vitro, unlike SPEA. This SLO-induced PMNL binding is dose-dependent and mediated by CD11/CD18 glycoproteins, offering insights into toxic shock mechanisms.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Autopsies reveal polymorphonuclear leukocyte (PMNL) accumulation in microvasculature during streptococcal toxic shock.
- Increased prevalence of streptococcal pyrogenic exotoxin A (SPEA)-producing strains correlates with toxic shock syndrome.
Purpose of the Study:
- To investigate whether SPEA or streptolysin O (SLO) stimulate PMNL-dependent adherence mechanisms in vitro.
- To elucidate the role of bacterial toxins in PMNL recruitment during streptococcal infections.
Main Methods:
- In vitro experiments exposing PMNL to varying concentrations of SPEA and SLO.
- Quantification of PMNL adherence to microvasculature.
- Analysis of adherence glycoprotein mediation, specifically CD11/CD18.
Main Results:
- SPEA showed only modest enhancement of PMNL adherence across tested concentrations.
- SLO induced a highly dose-dependent increase in PMNL binding, reaching maximal levels at 0.5 hemolytic units.
- SLO-mediated PMNL adherence was confirmed to be dependent on the CD11/CD18 adherence glycoprotein.
Conclusions:
- SLO is a potent stimulator of PMNL adherence in vitro, suggesting a significant role in the pathogenesis of streptococcal toxic shock.
- SPEA appears to have a limited role in directly promoting PMNL adherence compared to SLO.
- The CD11/CD18 glycoprotein pathway is crucial for SLO-induced PMNL recruitment.