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Volume 14 Supplement 2

Sepsis 2010

  • Poster presentation
  • Open Access

The new sepsis marker, sCD14-ST, induction mechanism in the rabbit sepsis models

  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Critical Care201014 (Suppl 2) :P19

https://doi.org/10.1186/cc9122

  • Published:

Keywords

  • Diagnostic Marker
  • Cytochalasin
  • Sepsis Patient
  • Soluble CD14
  • Cecal Ligation

Introduction

Soluble CD14 subtype (sCD14-ST) is a fragment of CD14 and is markedly increased in sepsis patients. We developed a new immunoassay to detect sCD14-ST and evaluated the efficacy of this marker for diagnosis of sepsis. For developing the strategies of sCD14-ST as a sepsis diagnostic marker, the induction mechanism must be known.

Methods

To determine the kinetics of sCD14-ST in the rabbit endotoxin shock model and the cecal ligation and puncture (CLP) model, we prepared the rabbit sCD14-ST immunoassay. Induction by inflammatory inducers and inhibition of sCD14-ST production were assessed using rabbit abdominal cavity granulocytes. Fragmentation of CD14 by N-aspartic protease was analyzed by western blot analysis and immunoassay.

Results

sCD14-ST was induced in the CLP model. However, sCD14-ST was not induced in the endotoxin shock model. These results suggested that sCD14-ST was not induced after stimulation by physiologic activating agent but induced by bacterial infection. sCD14-ST was not induced after stimulation of rabbit granulocytes by LPS, IFNγ, FMLP, and PMA. In contrast, it was induced by adding Escherichia coli, indicating that sCD14-ST is produced by phagocytosis rather than inflammation. The phagocytosis inhibitors cytochalasin D and wortomanin inhibited the production of sCD14-ST in vitro. Additionally, N-asparagin protease inhibitor inhibited the production of sCD14-ST from granulocytes. Additionally sCD14-ST was detected from recombinant CD14 digested supernatant by cathepsin D enzyme.

Conclusions

These data suggested that induction mechanism of sCD14-ST is dependent on the phagocytosis and cathepsin D is one of the enzymes for fragmentation of CD14. This mechanism is strong evidence for explanation of the production of sCD14-ST in sepsis patients.

Authors’ Affiliations

(1)
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd, Gotemba, Japan

Copyright

© BioMed Central Ltd 2010

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