Coagulation factor XII regulates inflammatory responses in human lungs

Rosanna Hess; Lukasz Wujak; Christina Hesse; Katherina Sewald; Danny Jonigk; Gregor Warnecke; Hans-Gerd Fieguth; Steven de Maat; Coen Maas; Francesco Bonella; Klaus T. Preissner; Benjamin Weiss; Liliana Schaefer; Wolfgang M. Kuebler; Philipp Markart; Malgorzata Wygrecka

doi:10.1160/TH16-12-0904

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany

,

Lukasz Wujak

¹Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany

,

Christina Hesse^†

⁴Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany

,

Katherina Sewald^†

⁴Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany

,

Danny Jonigk^†

⁵Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany

,

Gregor Warnecke^†

⁵Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany

,

Hans-Gerd Fieguth

⁶KRH Klinikum Oststadt-Heidehaus, Hannover, Germany

,

Steven de Maat

⁷Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands

,

Coen Maas

⁷Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands

,

Francesco Bonella

⁸Interstitial and Rare Lung Disease Unit, Ruhrland Hospital, University of Duisburg-Essen, Essen, Germany

,

Klaus T. Preissner^†

¹Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany

,

Benjamin Weiss

³Department of Surgery, Universities of Giessen and Marburg Lung Center, Giessen, Germany

,

Liliana Schaefer

⁹Goethe University School of Medicine, University Hospital, Frankfurt am Main, Germany

,

Wolfgang M. Kuebler

¹⁰Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada

¹¹Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

,

Philipp Markart^†

²Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany

,

Malgorzata Wygrecka^†

¹Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany

› Author Affiliations

Abstract

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

Full Text

References

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