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, Ourania Tsitsilonis

Research output: Contribution to journalArticlepeer-review

3 Citations (SciVal)

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 postinfection likely correlate with sepsis resolution and thus, the decapeptide could eventually serve as an early surrogate biomarker for predicting bacteria-induced sepsis outcome.

Original languageEnglish
Pages (from-to)48635-48649
Number of pages15
JournalOncotarget
Volume8
Issue number30
DOIs
Publication statusPublished - 24 May 2017

Keywords

  • Apoptosis
  • Biomarker
  • Immune response
  • Immunity
  • Immunology and Microbiology Section
  • Klebsiella pneumoniae
  • ProTα(100-109)
  • Sepsis

ASJC Scopus subject areas

  • Oncology

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