Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Sepsis results from an overwhelming response to infection and is a major contributor to death in intensive care units worldwide. In recent years, we and others have shown that neutrophil functionality is impaired in sepsis. This correlates with sepsis severity and contributes to aggravation of sepsis by precluding bacterial clearance. ⋯ We also demonstrate that inhibition of sGC activity increased survival in a murine model of sepsis, which was paralleled by restored neutrophil migratory function and increased bacterial clearance. Finally, the beneficial effect of sGC inhibition could also be demonstrated in mice treated after the onset of sepsis. Our results suggest that the beneficial effects of sGC inhibition in sepsis could be at least in part attributed to a recovery of neutrophil functionality.
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Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. ⋯ On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by S. pyogenes of the M1 serotype.