Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression

Erik Malmström; Alzbeta Davidova; Matthias Mörgelin; Adam Linder; Michael Larsen; Klaus Qvortrup; Pontus Nordenfelt; Oonagh Shannon; Olga Dzupova; Michal Holub; Johan Malmström; Heiko Herwald

doi:10.1160/th14-04-0312

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(06): 1230-1243
DOI: 10.1160/th14-04-0312

Wound Healing and Inflammation/Infection

Schattauer GmbH

Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression

Erik Malmström

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

,

Alzbeta Davidova

²Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic

³Department of Infectious Diseases, First Faculty of Medicine, Military University Hospital and Charles University in Prague, Prague, Czech Republic

,

Matthias Mörgelin

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

,

Adam Linder

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

⁴Centre for Heart Lung Innovation, St. Paul’s Hospital, The University of British Columbia (UBC), Vancouver, British Columbia, Canada

,

Michael Larsen

⁵Department of Biomedical Sciences, CFIM, The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

,

Klaus Qvortrup

⁵Department of Biomedical Sciences, CFIM, The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

,

Pontus Nordenfelt

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

⁶Springer Laboratory, Program in Cellular and Molecular Medicine, Children’s Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA

,

Oonagh Shannon

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

,

Olga Dzupova

⁷Department of Infectious Diseases, Third Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic

,

Michal Holub

²Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic

³Department of Infectious Diseases, First Faculty of Medicine, Military University Hospital and Charles University in Prague, Prague, Czech Republic

,

Johan Malmström

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

,

Heiko Herwald

¹Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden

› Author Affiliations

Abstract

Summary

Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation, an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil- derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis.

Keywords

Coagulation - infectious diseases - innate immunity - neutrophils - mass spectrometry - proteomics

Full Text

References

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