title: Vascular dysfunction and ischemic destruction of tissue in Streptococcus pyogenes infection: the role of streptolysin O-induced platelet/neutrophil complexes.
abstract: 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.
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center, Boise, ID 83702, USA. amy.bryant@mindspring.com
authors.forename: Amy E
authors.initials: AE
authors.lastname: Bryant
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Bayer
authors.forename: Richard Y Z
authors.initials: RY
authors.lastname: Chen
authors.forename: Paul H
authors.initials: PH
authors.lastname: Guth
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Wallace
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: 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*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019007:P-Selectin; D013301:Streptolysins; C025964:streptolysin O