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Coagulation factor XII regulates inflammatory responses in human lungs.

Abstract：

: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 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. 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.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Hess R,Wujak L,Hesse C,Sewald K,Jonigk D,Warnecke G,Fieguth HG,de Maat S,Maas C,Bonella F,Preissner KT,Weiss B,Schaefer L,Kuebler WM,Markart P,Wygrecka M

doi

10.1160/TH16-12-0904

subject

Has Abstract

pub_date

2017-10-05 00:00:00

pages

1896-1907

issue

10

eissn

0340-6245

issn

2567-689X

pii

16-12-0904

journal_volume

117

pub_type

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