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Mediators of Inflammation
Volume 2016 (2016), Article ID 6129437, 13 pages
http://dx.doi.org/10.1155/2016/6129437
Research Article

C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function

1Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
2Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Albert-Einstein-Street 10, 07745 Jena, Germany
3Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
4Department of Anesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
5Department for Medical Microbiology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
6Paul-Martini-Research Group, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
7Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Brühler Street 7, 53119 Bonn, Germany

Received 11 December 2015; Revised 29 February 2016; Accepted 16 May 2016

Academic Editor: Pham My-Chan Dang

Copyright © 2016 Nancy Blaurock et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis.