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Thromb Haemost 2017; 117(10): 1896-1907
DOI: 10.1160/TH16-12-0904
Blood Cells, Inflammation and Infection
Schattauer GmbH

Coagulation factor XII regulates inflammatory responses in human lungs

Rosanna Hess
1   Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany
,
Lukasz Wujak
1   Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany
,
Christina Hesse   †
4   Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
,
Katherina Sewald   †
4   Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
,
Danny Jonigk   †
5   Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
,
Gregor Warnecke   †
5   Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany
,
Hans-Gerd Fieguth
6   KRH Klinikum Oststadt-Heidehaus, Hannover, Germany
,
Steven de Maat
7   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Coen Maas
7   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Francesco Bonella
8   Interstitial and Rare Lung Disease Unit, Ruhrland Hospital, University of Duisburg-Essen, Essen, Germany
,
Klaus T. Preissner   †
1   Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany
,
Benjamin Weiss
3   Department of Surgery, Universities of Giessen and Marburg Lung Center, Giessen, Germany
,
Liliana Schaefer
9   Goethe University School of Medicine, University Hospital, Frankfurt am Main, Germany
,
Wolfgang M. Kuebler
10   Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada
11   Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
,
Philipp Markart   †
2   Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany
,
Malgorzata Wygrecka   †
1   Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany
› Author Affiliations Financial support: This study was funded by the German Research Foundation (SFB/TR84 Project A2 to M. W. and K. T.P), the Else Kröner-Fresenius-Foundation (to M. W. and P. M.), the Oskar Helene Heim Foundation (to P. M.), the German Center for Lung Research (to M. W.) and the University Medical Center Giessen and Marburg (UKGM to M. W. and P. M.).
Further Information

Publication History

Received: 01 December 2016

Accepted after major revision: 23 June 2017

Publication Date:
08 November 2017 (online)

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Summary

Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array. Activation of the contact system, associated with high levels of coagulation factor XIIa (Hageman factor, FXIIa), plasma kallikrein and bradykinin, occurred rapidly in ARDS lungs after the onset of the disease and virtually normalized within one week from time of diagnosis. FXII levels in BALF were higher in ARDS nonsurvivors than survivors and were positively correlated with tumor necrosis factor (TNF)-α concentration. FXII induced the production and release of interleukin (IL)-8, IL-1β, IL-6, leukemia inhibitory factor (LIF), CXCL5 and TNF-α in human PCLS in a kallikrein-kinin-independent manner. In conclusion, accumulation of FXII in ARDS lungs may contribute to the release of pro-inflammatory mediators and is associated with clinical outcome. FXII inhibition may thus offer a novel and promising therapeutic approach to antagonize overwhelming inflammatory responses in ARDS lungs without interfering with vital haemostasis.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Acute respiratory distress syndrome - contact phase system - coagulation factor XII

† Member of the German Center for Lung Research.


 

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