Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions impede neutrophil diapedesis

Comparative analysis of lesions caused by histotoxic clostridia in experimentally induced myonecrosis

“…In addition, inflammatory infiltration is effectively immobilized and destroyed by the toxins (VAN VLEET;VALENTINE, 2007). The paucity of phagocytic cells in guinea pigs inoculated with C. perfringens type A in the area of the infection could be mediated by the cytotoxic effects of perfringolisin O on leukocytes and by the ability of alpha toxin to activate synthesis of cell adhesion molecules, causing neutrophils to adhere and migration at remote locations from the site of infection that impede neutrophil diapedesis (BRYANT et al, 2006). The low inflammatory infiltrated observed in guinea pigs inoculated with C. novyi type A, and C. sordellii could be explained by apoptotic process induced by major toxins (JUST; GERHARD, 2004).…”

“…Furthermore, the toxin promotes platelet aggregation and vasoconstriction which leads to thrombosis and subsequent tissue anoxia (HICKEY et al, 2008). Possibly, in addition to its direct necrotizing action, the alpha toxin induced rapid and irreversible reduction of blood flow with greater intensity producing marked muscle ischemia, which probably led to liquefactive necrosis in guinea pigs inoculated with this agent (BRYANT et al, 2006). Floccular necrosis ( Figure 2B) was the predominant lesion in guinea pigs inoculated with C. sordellii and C. novyi type A. C. sordellii produces several virulence factors, but the major are the lethal toxin, and a hemorrhagic toxin.…”

‘Flesh-eating’ necrotizing infections: must we amputate?

“…The q toxin of C. perfringens (known as perfringolysin O) also contributes to aggregate formation and aggregate-mediated vascular occlusion. Specifically, q toxin functionally upregulates adhesins on both platelets and leukocytes [4,9], which promotes their co-aggregation and facilitates their tethering to the activated vascular endothelium [9]. We have subsequently shown that streptolysin O (SLO; a cholesteroldependent cytolysin homologous to C. perfringens perfringolysin O) also induces the co-aggregation of platelets and neutrophils and that SLO-induced intravascular platelet/leukocyte aggregates also contribute to tissue destruction [10].…”

“…Without adequate inflammatory infiltration into infected tissues, bacterial replication proceeds unchecked. In C. perfringens gas gangrene and likely in group A streptococcal myonecrosis, the absence of a tissue inflammatory response is also mediated by toxin-induced disruption of the functional platelet/neutrophil/ endothelial axis [4].…”

“…Our recent studies have shown that within minutes, PLC stimulates the formation of large intravascular aggregates of platelets and leukocytes that irreversibly block blood flow [6,7] and impair leukocyte extravasation into infected tissues [4,8]. The q toxin of C. perfringens (known as perfringolysin O) also contributes to aggregate formation and aggregate-mediated vascular occlusion.…”