Coagulation factor XII regulates inflammatory responses in human lungs

被引：47

作者：

Hess, Rosanna ^{[1
]}

Wujak, Lukasz ^{[1
]}

Hesse, Christina ^{[4
]}

Sewald, Katherina ^{[4
]}

Jonigk, Danny ^{[5
]}

Warnecke, Gregor ^{[5
]}

Fieguth, Hans-Gerd ^{[6
]}

de Maat, Steven ^{[7
]}

Maas, Coen ^{[7
]}

Bonella, Francesco ^{[8
]}

Preissner, Klaus T. ^{[1
]}

Weiss, Benjamin ^{[3
]}

Schaefer, Liliana ^{[9
]}

Kuebler, Wolfgang M. ^{[10
,11
]}

Markart, Philipp ^{[2
]}

Wygrecka, Malgorzata ^{[1
]}

机构：

[1] Univ Giessen & Marburg Lung Ctr, Dept Biochem, Giessen, Germany

[2] Univ Giessen & Marburg Lung Ctr, Dept Internal Med, Giessen, Germany

[3] Univ Giessen & Marburg Lung Ctr, Dept Surg, Giessen, Germany

[4] Fraunhofer Inst Toxicol & Expt Med ITEM, Hannover, Germany

[5] Hannover Med Sch, Dept Cardiac Thorac Transplantat & Vasc Surg, Hannover, Germany

[6] KRH Klinikum Oststadt Heidehaus, Hannover, Germany

[7] Univ Med Ctr Utrecht, Dept Clin Chem & Haematol, Utrecht, Netherlands

[8] Univ Duisburg Essen, Ruhrland Hosp, Interstitial & Rare Lung Dis Unit, Essen, Germany

[9] Goethe Univ, Univ Hosp, Sch Med, Frankfurt, Germany

[10] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada

[11] Charite, Inst Physiol, Berlin, Germany

来源：

THROMBOSIS AND HAEMOSTASIS | 2017年 / 117卷 / 10期

关键词：

Acute respiratory distress syndrome; contact phase system; coagulation factor XII; RESPIRATORY-DISTRESS-SYNDROME; MONOCYTE CHEMOTACTIC ACTIVITY; ACTIVATED FACTOR-XII; BLOOD-COAGULATION; CONTACT SYSTEM; SYNDROME ARDS; RELEASE NEUTROPHIL; ENDOTHELIAL-CELLS; EXPRESSION; CYTOKINES;

D O I：

10.1160/TH16-12-0904

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 Xlla (Hageman factor, FXlla), 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)-alpha concentration. FXII induced the production and release of interleukin (IL)-8, IL-1 beta, IL-6, leukemia inhibitory factor (LIF), CXCL5 and TNF-alpha 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.

引用

页码：1896 / 1907

页数：12

共 37 条

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