Oncotarget

Research Papers: Immunology:

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

Pinelopi Samara, Vivi Miriagou, Michael Zachariadis, Olga Mavrofrydi, Vasilis J. Promponas, Skarlatos G. Dedos, Panagiota Papazafiri, Hubert Kalbacher, Wolfgang Voelter and Ourania Tsitsilonis _

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Oncotarget. 2017; 8:48635-48649. https://doi.org/10.18632/oncotarget.18149

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Abstract

Pinelopi Samara1, Vivi Miriagou2, Michael Zachariadis1,3, Olga Mavrofrydi1, Vasilis J. Promponas4, Skarlatos G. Dedos1, Panagiota Papazafiri1, Hubert Kalbacher5, Wolfgang Voelter5 and Ourania Tsitsilonis1

1 Department of Biology, National and Kapodistrian University of Athens, Athens, Greece

2 Laboratory of Bacteriology, Hellenic Pasteur Institute, Athens, Greece

3 Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, Agia Paraskevi, Athens, Greece

4 Bioinformatics Research Laboratory, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus

5 Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany

Correspondence to:

Ourania Tsitsilonis, email:

Pinelopi Samara, email:

Keywords: apoptosis, biomarker, Klebsiella pneumoniae, proTα(100-109), sepsis, Immunology and Microbiology Section, Immune response, Immunity

Received: December 15, 2016 Accepted: April 17, 2017 Published: May 24, 2017

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.


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