{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T07:52:31Z","timestamp":1724399551027},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,5,25]],"date-time":"2011-05-25T00:00:00Z","timestamp":1306281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> In malaria and sepsis, apoptotic endothelial damage is preventable <jats:italic>in vitro<\/jats:italic> by antioxidants and protease inhibitors. Activated protein C, which has anti\u2010apoptotic effects, improves survival in sepsis. Therefore, we studied whether activated protein C prevents endothelial cell apoptosis, induced by serum from patients with malaria or sepsis.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> Endothelial cells were incubated with patient sera (<jats:italic>Plasmodium falciparum<\/jats:italic> malaria, <jats:italic>Escherichia coli<\/jats:italic> sepsis, <jats:italic>Staphylococcus aureus<\/jats:italic> sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Activated protein C was used to reduce endothelial cell apoptosis <jats:italic>in vitro<\/jats:italic>. The proportion of apoptotic endothelial cells was determined by TUNEL staining.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> The apoptosis\u2010inducing effect of patient sera or culture supernatants (<jats:italic>P.\u00a0falciparum<\/jats:italic>, <jats:italic>E.\u00a0coli<\/jats:italic>, <jats:italic>S.\u00a0aureus<\/jats:italic>) on endothelial cells was augmented by neutrophils and reduced by activated protein C in the presence of neutrophils. Pre\u2010incubating either endothelial cells or neutrophils with activated protein C also reduced the endothelial cell apoptosis rate. The pro\u2010apoptotic effect of <jats:italic>P.\u00a0falciparum<\/jats:italic> supernatant was reduced by pan\u2010caspase inhibitor and caspase 8 inhibitor, but not by caspase 9 inhibitor. The pro\u2010apoptotic effect of <jats:italic>E.\u00a0coli<\/jats:italic> and <jats:italic>S.\u00a0aureus<\/jats:italic> supernatants was also reduced by caspase 9 inhibitor.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Activated protein C protects vascular endothelial cells from apoptosis triggered by patient sera or culture supernatants in combination with neutrophils. It seems to act both on neutrophils and on endothelial cells. Activated protein C blocks caspase\u20108\u2010dependent apoptosis, which accounts for endothelial damage in sepsis and malaria. Therefore, activated protein C might offer clinical benefit not only in sepsis but also in malaria.<\/jats:p>","DOI":"10.1111\/j.1365-3156.2011.02788.x","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T01:34:37Z","timestamp":1306373677000},"page":"906-913","source":"Crossref","is-referenced-by-count":6,"title":["Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis"],"prefix":"10.1111","volume":"16","author":[{"given":"Christoph 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