Identification of a 14kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis

• Published in: Journal of pharmaceutical and biomedical analysis 2013-05, Vol.78-79, p.45-51
• Main Authors: De Freitas Caires, Nathalie, Legendre, Benjamin, Parmentier, Erika, Scherpereel, Arnaud, Tsicopoulos, Anne, Mathieu, Daniel, Lassalle, Philippe
• Format: Article
• Language: English
• Subjects: amino acids; Biomarker; biomarkers; Cathepsin G; death; distress; elastase; Endocan; endothelial cells; Endothelium; Immunoassay; immunoassays; neutrophils; pathogenesis; patients; polypeptides; proteolysis; Sepsis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2013.01.035

[Display omitted] ► Endocan is cleaved in a 14kDa fragment, named p14, specifically by cathepsin G. ► The 14kDa endocan fragment is circulating in plasma from patients with sepsis. ► An immunoassay specific for the p14 endocan fragment was developed. ► The p14 plasma levels are increased in patients with severe sepsis. ► p14 represents a novel interesting biomarker of sepsis. Severe septic syndrome, which is the most prevalent and lethal cause of acute respiratory distress syndrome, remains one of the most frequent causes of admission and death in intensive care units (ICU). Inflammatory phenomenon leading to severe sepsis are multiple and not yet completely understood. The main target damage during severe sepsis is the endothelium. Endocan, specifically secreted by activated-pulmonary vascular endothelial cells, is thought to play a key role in the control of the lung inflammatory reaction. A recent clinical investigation found that a low plasma endocan level was predictive of respiratory failure. In this study, the hypothesis that low levels of endocan may result from proteolysis was tested. We demonstrate that cathepsin G (CG), neutrophil elastase (NE), and to a lesser extent proteinase 3 (PR3), degrade endocan. Interestingly, a novel endocan peptide fragment of 14kDa, named p14, was identified, resulting from the specific cleavage of endocan by CG, corresponding to the N-terminal 111–116 amino acids of the endocan polypeptide. An immunoassay specific for p14 endocan fragment was then developed, and revealed increased plasma levels of p14 in 20 out of 55 severe septic patients, ranging from 0.52 to 10.40ng/mL versus undetectable p14 in plasma from 32 control subjects (p=0.0011). No correlations were found between p14 and endocan blood levels in severe septic patients. Taken together, the p14 endocan fragment represents a novel interesting biomarker which could participate to the pathogenesis of sepsis.