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A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis.

TitleA fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis.
Publication TypeJournal Article
Year of Publication2017
AuthorsSamara, Pinelopi, Vivi Miriagou, Michael Zachariadis, Olga Mavrofrydi, V. J. Promponas, Skarlatos G. Dedos, Panagiota Papazafiri, Hubert Kalbacher, Wolfgang Voelter, and Ourania Tsitsilonis
JournalOncotarget
Volume8
Issue30
Pagination48635-48649
Date Published2017 Jul 25
ISSN1949-2553
KeywordsAnimals, Apoptosis, Biomarkers, Disease Models, Animal, Female, Klebsiella Infections, Klebsiella pneumoniae, Macrophages, Mice, Monocytes, Mortality, Phagocytosis, Protein Precursors, Sepsis, Thymosin
Abstract

Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides related to cell death. In this study, we generated bacterial models of sepsis in mice using two Klebsiella pneumoniae strains (L-78 and ATCC 43816) and monitored sepsis progression using proTα(100-109) as a biomarker. Serum concentration of proTα(100-109) gradually increased as sepsis progressed in mice infected with L-78, a strain which, unlike ATCC 43816, was phagocytosed by monocytes/macrophages. Analysis of splenocytes from L-78-infected animals revealed that post-infection spleen monocytes/macrophages were gradually driven to caspase-3-mediated apoptosis. These results were verified in vitro in L-78-infected human monocytes/macrophages. Efficient phagocytosis of L-78 by monocytes stimulated their apoptosis and the concentration of proTα(100-109) in culture supernatants increased. Human macrophages strongly phagocytosed L-78, but resisted cell death. This is the first report suggesting that high levels of proTα(100-109) correlate, both in vitro and in vivo, with increased percentages of cell apoptosis. Moreover, we showed that low levels of proTα(100-109) early post-infection likely correlate with sepsis resolution and thus, the decapeptide could eventually serve as an early surrogate biomarker for predicting bacteria-induced sepsis outcome.

DOI10.18632/oncotarget.18149
Alternate JournalOncotarget


by Dr. Radut.