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Interaction of fact...
Interaction of factor VII activating protease (FSAP) with neutrophil extracellular traps (NETs)
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- Grasso, Simona (author)
- Oslo university hospital
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- Neumann, Ariane (author)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,University of Veterinary Medicine Hannover
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- Lang, Irene M. (author)
- Medical University of Vienna
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- Etscheid, Michael (author)
- Paul Ehrlich Institute
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- von Köckritz-Blickwede, Maren (author)
- University of Veterinary Medicine Hannover
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- Kanse, Sandip M. (author)
- Oslo university hospital
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English 7 s.
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 161, s. 36-42
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Abstract
Subject headings
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- The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP. Plasma-derived FSAP as well as exogenous FSAP bound to NETs. There was co-localization of FSAP and NETs in coronary thrombi from patients with acute myocardial infarction. Contrary to our expectations no activation of pro-FSAP by NETs was evident. However, after disintegration of NETs with DNase, a robust activation of pro-FSAP, due to release of histones from nucleosomes, was detected. The released histones were in turn degraded by FSAP. Histone cytotoxicity towards endothelial cells was neutralized by FSAP more potently than by activated protein C (APC). One more consequence of histone degradation was a decrease in nucleosome release from apoptotic neutrophils. Taken together, NETs bind to FSAP, but do not activate pro-FSAP unless histones are released from NETs by DNAse. This activation of FSAP is likely to be important in diminishing the cytotoxic effect of histones, thus limiting the damaging effect of NETosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- FSAP
- Inflammation
- NETs
- Thrombosis
Publication and Content Type
- art (subject category)
- ref (subject category)
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