Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598420
Freie Vorträge – Sektion Zellbiologie
Klinische und experimentelle Grundlagenforschung – Robert Bals/Homburg (Saar), Michael Wegmann/Borstel
Georg Thieme Verlag KG Stuttgart · New York

Hageman Factor regulates inflammatory responses in ARDS

M Wygrecka
1   Department of Biochemistry, Universities of Gießen and Marburg Lung Center
,
R Hess
1   Department of Biochemistry, Universities of Gießen and Marburg Lung Center
,
L Wujak
1   Department of Biochemistry, Universities of Gießen and Marburg Lung Center
,
C Hesse
2   Fraunhofer Institute for Toxicology and Experimental Medicine Item, Hannover
,
K Sewald
2   Fraunhofer Institute for Toxicology and Experimental Medicine Item, Hannover
,
S de Maat
3   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, the Netherlands
,
C Maas
3   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, the Netherlands
,
F Bonella
4   Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, University Duisburg-Essen
,
P Markart
5   Universitätsklinikum Gießen und Marburg GmbH
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)

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Rationale:

Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact system of coagulation is activated and may regulate inflammatory responses in ARDS lungs.

Methods:

Components of the contact 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.

Measurements and Main Results:

Activation of the contact system, associated with high levels of Hageman factor (FXII), plasma kallikrein and bradykinin, in ARDS lungs occurred rapidly after the onset of the disease and virtually normalized within one week from time of diagnosis. FXII levels in BALF were higher in ARDS non-survivors 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.

Conclusions:

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 hemostasis.