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

TY - JOUR

T1 - Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression

AU - Malmström, E

AU - Davidova, A

AU - Mörgelin, M

AU - Linder, A

AU - Larsen, Michael

AU - Qvortrup, Klaus

AU - Nordenfelt, P

AU - Shannon, O

AU - Dzupova, O

AU - Holub, M

AU - Malmström, J

AU - Herwald, H

PY - 2014/8/7

Y1 - 2014/8/7

N2 - 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.

AB - 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.

U2 - 10.1160/th14-04-0312

DO - 10.1160/th14-04-0312

M3 - Journal article

C2 - 25104417

SN - 0340-6245

VL - 112

SP - 1230

EP - 1243

JO - Thrombosis et diathesis haemorrhagica

JF - Thrombosis et diathesis haemorrhagica

IS - 6

ER -