Inflammation research : official journal of the European Histamine Research Society ... [et al.]
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The present study aimed to investigate the combined effects of a neutrophil elastase inhibitor, sivelestat sodium, with a free radical scavenger, edaravone, on lipolysaccharide (LPS)-induced acute lung injury (ALI). ⋯ Combination of sivelestat and edaravone shows promise as a new treatment option for ALI/acute respiratory distress syndrome patients.
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Platelets promote sepsis-induced activation of neutrophils via secretion of CD40L. However, the mechanism regulating the release of platelet-derived CD40L is not known. We hypothesized that matrix metalloproteinases (MMPs) might regulate shedding of platelet-expressed CD40L and neutrophil activation in sepsis. ⋯ We describe a novel role of metalloproteinases in regulating platelet-dependent activation and infiltration of neutrophils in septic lung injury which might be related to controlling CD40L shedding from platelets. We conclude that targeting metalloproteinases may be a useful strategy for limiting acute lung injury in abdominal sepsis.