Download PDF
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)

Also available at
    Permissions and Reprints

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.


 

  • References

  • 1 Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 2010; 23: 243-252.
    CrossrefPubMedGoogle Scholar
  • 2 Reiss LK, Uhlig U, Uhlig S. Models and mechanisms of acute lung injury caused by direct insults. Eur J Cell Biol 2012; 91: 590-601.
    CrossrefPubMedGoogle Scholar
  • 3 Baron RM, Levy BD. Recent advances in understanding and treating ARDS. F1000Res. 2016 05..
    PubMedGoogle Scholar
  • 4 Blondonnet R, Constantin JM, Sapin V. et al. A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome. Dis Markers 2016; 2016: 3501373.
    PubMedGoogle Scholar
  • 5 Toossi Z, Sedor JR, Mettler MA. et al. Induction of expression of monocyte interleukin 1 by Hageman factor (factor XII). Proc Natl Acad Sci USA 1992; 89: 11969-11972.
    CrossrefPubMedGoogle Scholar
  • 6 Wachtfogel YT, Pixley RA, Kucich U. et al. Purified plasma factor XIIa aggregates human neutrophils and causes degranulation. Blood 1986; 67: 1731-1737.
    PubMedGoogle Scholar
  • 7 Khan MM, Bradford HN, Isordia-Salas I. et al. High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes. Arterioscler Thromb Vasc Biol 2006; 26: 2260-2266.
    CrossrefPubMedGoogle Scholar
  • 8 Velasco F, Torres A, Guerrero A. et al. Behaviour of the contact phase of blood coagulation in the adult respiratory distress syndrome (ARDS). Thromb Haemost 1986; 55: 357-360.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Herrera C, Velasco F, Guerrero A. et al. Contact phase of blood coagulation in cardiogenic pulmonary oedema (CPO) and adult respiratory distress syndrome (ARDS). Intensive Care Med 1989; 15: 99-104.
    CrossrefPubMedGoogle Scholar
  • 10 Carvalho AC, DeMarinis S, Scott CF. et al. Activation of the contact system of plasma proteolysis in the adult respiratory distress syndrome. J Lab Clin Med 1988; 112: 270-277.
    PubMedGoogle Scholar
  • 11 de Oliveira GG, Antonio MP. Adult respiratory distress syndrome (ARDS): the pathophysiologic role of catecholamine-kinin interactions. J Trauma 1988; 28: 246-253.
    CrossrefPubMedGoogle Scholar
  • 12 Coppola R, Cristilli P, Cugno M. et al. Measurement of activated factor XII in health and disease. Blood Coagul Fibrinolysis 1996; 07: 530-535.
    CrossrefPubMedGoogle Scholar
  • 13 Persson K, Morgelin M, Lindbom L. et al. Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system. J Exp Med 2000; 192: 1415-1424.
    CrossrefPubMedGoogle Scholar
  • 14 Tucker EI, Verbout NG, Leung PY. et al. Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis. Blood 2012; 119: 4762-4768.
    CrossrefPubMedGoogle Scholar
  • 15 Ranieri VM, Rubenfeld GD, Thompson BT. et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307: 2526-2533.
    PubMedGoogle Scholar
  • 16 Vorlova S, Koch M, Manthey HD. et al. Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice. Thromb Haemost 2017; 117: 176-187.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Gobel K, Pankratz S, Asaridou CM. et al. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nat Commun 2016; 07: 11626.
    CrossrefPubMedGoogle Scholar
  • 18 LaRusch GA, Mahdi F, Shariat-Madar Z. et al. Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis. Blood 2010; 115: 5111-5120.
    CrossrefPubMedGoogle Scholar
  • 19 Shi JX, Su X, Xu J. et al. MK2 posttranscriptionally regulates TNF-alpha-induced expression of ICAM-1 and IL-8 via tristetraprolin in human pulmonary microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 2012; 302: L793-L799.
    CrossrefPubMedGoogle Scholar
  • 20 Pugin J, Ricou B, Steinberg KP. et al. Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1. Am J Respir Crit Care Med 1996; 153: 1850-1856.
    CrossrefPubMedGoogle Scholar
  • 21 Oikonomopoulou K, Ricklin D, Ward PA. et al. Interactions between coagulation and complement--their role in inflammation. Semin Immunopathol 2012; 34: 151-165.
    CrossrefPubMedGoogle Scholar
  • 22 Ghebrehiwet B, Silverberg M, Kaplan AP. Activation of the classical pathway of complement by Hageman factor fragment. J Exp Med 1981; 153: 665-676.
    CrossrefPubMedGoogle Scholar
  • 23 Broadley KJ, Blair AE, Kidd EJ. et al. Bradykinin-induced lung inflammation and bronchoconstriction: role in parainfluenze-3 virus-induced inflammation and airway hyperreactivity. J Pharmacol Exp Ther 2010; 335: 681-692.
    CrossrefPubMedGoogle Scholar
  • 24 Ridings PC, Blocher CR, Fisher BJ. et al. Beneficial effects of a bradykinin antagonist in a model of gram-negative sepsis. J Trauma 1995; 39: 81-89.
    CrossrefPubMedGoogle Scholar
  • 25 Koyama S, Sato E, Nomura H. et al. Bradykinin stimulates type II alveolar cells to release neutrophil and monocyte chemotactic activity and inflammatory cytokines. Am J Pathol 1998; 153: 1885-1893.
    CrossrefPubMedGoogle Scholar
  • 26 Koyama S, Sato E, Numanami H. et al. Bradykinin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity. Am J Respir Cell Mol Biol 2000; 22: 75-84.
    CrossrefPubMedGoogle Scholar
  • 27 Deng X, Wang X, Andersson R. Endothelial barrier resistance in multiple organs after septic and nonseptic challenges in the rat. J Appl Physiol 1995; 78: 2052-2061.
    CrossrefPubMedGoogle Scholar
  • 28 Meduri GU, Kohler G, Headley S. et al. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995; 108: 1303-1314.
    CrossrefPubMedGoogle Scholar
  • 29 Wachtfogel YT, Kucich U, James HL. et al. Human plasma kallikrein releases neutrophil elastase during blood coagulation. J Clin Invest 1983; 72: 1672-1677.
    CrossrefPubMedGoogle Scholar
  • 30 Itakura A, Verbout NG, Phillips KG. et al. Activated factor XI inhibits chemotaxis of polymorphonuclear leukocytes. J Leukoc Biol 2011; 90: 923-927.
    CrossrefPubMedGoogle Scholar
  • 31 Bane Jr CE, Ivanov I, Matafonov A. et al. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice. PLoS One 2016; 11: e0152968.
    CrossrefPubMedGoogle Scholar
  • 32 White-Adams TC, Berny MA, Tucker EI. et al. Identification of coagulation factor XI as a ligand for platelet apolipoprotein E receptor 2 (ApoER2). Arterioscler Thromb Vasc Biol 2009; 29: 1602-1607.
    CrossrefPubMedGoogle Scholar
  • 33 Pixley RA, De La Cadena R, Page JD. et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 91: 61-68.
    CrossrefPubMedGoogle Scholar
  • 34 Iwaki T, Cruz-Topete D, Castellino FJ. A complete factor XII deficiency does not affect coagulopathy, inflammatory responses, and lethality, but attenuates early hypotension in endotoxemic mice. J Thromb Haemost 2008; 06: 1993-1995.
    CrossrefPubMedGoogle Scholar
  • 35 Lener M, Vinci G, Duponchel C. et al. Molecular cloning, gene structure and expression profile of mouse C1 inhibitor. Eur J Biochem 1998; 254: 117-122.
    CrossrefPubMedGoogle Scholar
  • 36 Schousboe I. Binding of activated Factor XII to endothelial cells affects its inactivation by the C1-esterase inhibitor. Eur J Biochem 2003; 270: 111-118.
    PubMedGoogle Scholar
  • 37 Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol 2011; 06: 147-163.
    CrossrefPubMedGoogle Scholar