Vascular dysfunction and ischemic destruction of tissue in Streptococcus pyogenes infection: the role of streptolysin O-induced platelet/neutrophil complexes.
Rapid tissue destruction in group A streptococcal (GAS) necrotizing fasciitis/myonecrosis often necessitates extensive debridement to ensure survival. The mechanisms responsible for this fulminant process remain unknown; we hypothesized that toxin-induced ischemia contributes to necrosis. In a rat model, Doppler flowmetry was used to measure local blood flow at the site of the intramuscular injection of exotoxins from an invasive M-type 1 GAS, which caused a rapid, dose-dependent decrease in perfusion that was irreversible at the highest toxin concentration tested. Videomicroscopic results revealed that blood flow was impeded by occlusive intravascular cellular aggregates. Flow-cytometric results confirmed that GAS toxins induced the coaggregation of platelets and neutrophils, that this activity was attributable to streptolysin O, and that platelet/neutrophil complex formation was largely mediated by platelet P-selectin (CD62P). Strategies that target platelet adherence molecules may prevent vascular occlusion, maintain tissue viability, and reduce the need for amputation in necrotizing GAS infections.
Bryant
Amy E
AE
Infectious Diseases Section, Veterans Affairs Medical Center, Boise, ID 83702, USA. amy.bryant@mindspring.com
Bayer
Clifford R
CR
Chen
Richard Y Z
RY
Guth
Paul H
PH
Wallace
Randi J
RJ
Stevens
Dennis L
DL
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology / Q000633:toxicity; D001427:Bacterial Toxins / Q000633:toxicity; D001792:Blood Platelets / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology* / Q000503:physiopathology; D002449:Cell Aggregation; D004195:Disease Models, Animal; D019115:Fasciitis, Necrotizing / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013290:Streptococcal Infections / Q000473:pathology* / Q000503:physiopathology*; D013297:Streptococcus pyogenes; D013301:Streptolysins / Q000502:physiology* / Q000633:toxicity*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019007:P-Selectin; D013301:Streptolysins; C025964:streptolysin O