A Role for Bronchial Epithelial Autotaxin in Ventilator-induced Lung Injury

Overview

Journal Intensive Care Med Exp

Specialty Critical Care

Date 2021 Mar 29

PMID 33778909

Citations 3

Authors

Ioanna Nikitopoulou

Ioanna Ninou

Nikolaos Manitsopoulos

Ioanna Dimopoulou

Stylianos E Orfanos

Vassilis Aidinis

Anastasia Kotanidou

Affiliations

Soon will be listed here.

Abstract

Background: The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ventilator-induced lung injury (VILI). Autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular lysophosphatidic acid (LPA) production, has been suggested to play a pathogenic role in, among others, pulmonary inflammation and fibrosis.

Methods: C57BL/6 mice were subjected to low and high tidal volume mechanical ventilation using a small animal ventilator: respiratory mechanics were evaluated, and plasma and bronchoalveolar lavage fluid (BALF) samples were obtained. Total protein concentration was determined, and lung histopathology was further performed RESULTS: Injurious ventilation resulted in increased BALF levels of ATX. Genetic deletion of ATX from bronchial epithelial cells attenuated VILI-induced pulmonary edema.

Conclusion: ATX participates in VILI pathogenesis.

Citing Articles

Decrease in serum levels of autotaxin in COVID-19 patients.

Shimura T, Kurano M, Okamoto K, Jubishi D, Hashimoto H, Kano K Ann Med. 2022; 54(1):3189-3200.

PMID: 36369824 PMC: 9665086. DOI: 10.1080/07853890.2022.2143554.

[Value of autotaxin in predicting refractory pneumonia in children and its correlation with inflammatory cytokines].

Fu B, Zhong L, Ye T, Han Y, Qiu X Zhongguo Dang Dai Er Ke Za Zhi. 2022; 24(7):765-770.

PMID: 35894191 PMC: 9336629. DOI: 10.7499/j.issn.1008-8830.2203030.

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target.

Ntatsoulis K, Karampitsakos T, Tsitoura E, Stylianaki E, Matralis A, Tzouvelekis A Front Immunol. 2021; 12:687397.

PMID: 34671341 PMC: 8522582. DOI: 10.3389/fimmu.2021.687397.

References

Matute-Bello G, Downey G, Moore B, Groshong S, Matthay M, Slutsky A . An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011; 44(5):725-38. PMC: 7328339. DOI: 10.1165/rcmb.2009-0210ST. View

Ganguly K, Stoeger T, Wesselkamper S, Reinhard C, Sartor M, Medvedovic M . Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure. Physiol Genomics. 2007; 31(3):410-21. DOI: 10.1152/physiolgenomics.00260.2006. View

Dreyfuss D, Saumon G . Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998; 157(1):294-323. DOI: 10.1164/ajrccm.157.1.9604014. View

Ninou I, Kaffe E, Muller S, Budd D, Stevenson C, Ullmer C . Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. Pulm Pharmacol Ther. 2018; 52:32-40. DOI: 10.1016/j.pupt.2018.08.003. View

Fotopoulou S, Oikonomou N, Grigorieva E, Nikitopoulou I, Paparountas T, Thanassopoulou A . ATX expression and LPA signalling are vital for the development of the nervous system. Dev Biol. 2010; 339(2):451-64. DOI: 10.1016/j.ydbio.2010.01.007. View

Bates J, Rincon M, Irvin C . Animal models of asthma. Am J Physiol Lung Cell Mol Physiol. 2009; 297(3):L401-10. PMC: 2739768. DOI: 10.1152/ajplung.00027.2009. View

Ren H, Panchatcharam M, Mueller P, Escalante-Alcalde D, Morris A, Smyth S . Lipid phosphate phosphatase (LPP3) and vascular development. Biochim Biophys Acta. 2012; 1831(1):126-32. PMC: 3683602. DOI: 10.1016/j.bbalip.2012.07.012. View

Nieman G, Andrews P, Satalin J, Wilcox K, Kollisch-Singule M, Madden M . Acute lung injury: how to stabilize a broken lung. Crit Care. 2018; 22(1):136. PMC: 5968707. DOI: 10.1186/s13054-018-2051-8. View

Chimenti L, Luque T, Bonsignore M, Ramirez J, Navajas D, Farre R . Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury. Eur Respir J. 2012; 40(4):939-48. DOI: 10.1183/09031936.00153211. View

10.

Oikonomou N, Mouratis M, Tzouvelekis A, Kaffe E, Valavanis C, Vilaras G . Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2012; 47(5):566-74. DOI: 10.1165/rcmb.2012-0004OC. View

11.

Fan E, Brodie D, Slutsky A . Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018; 319(7):698-710. DOI: 10.1001/jama.2017.21907. View

12.

Manali E, Moschos C, Triantafillidou C, Kotanidou A, Psallidas I, Karabela S . Static and dynamic mechanics of the murine lung after intratracheal bleomycin. BMC Pulm Med. 2011; 11:33. PMC: 3128859. DOI: 10.1186/1471-2466-11-33. View

13.

Ko Y, Yang M, Huang H, Hsu C, Chen L . NF-κB activation in myeloid cells mediates ventilator-induced lung injury. Respir Res. 2013; 14:69. PMC: 3708752. DOI: 10.1186/1465-9921-14-69. View

14.

Ninou I, Magkrioti C, Aidinis V . Autotaxin in Pathophysiology and Pulmonary Fibrosis. Front Med (Lausanne). 2018; 5:180. PMC: 6008954. DOI: 10.3389/fmed.2018.00180. View

15.

Mouratis M, Magkrioti C, Oikonomou N, Katsifa A, Prestwich G, Kaffe E . Autotaxin and Endotoxin-Induced Acute Lung Injury. PLoS One. 2015; 10(7):e0133619. PMC: 4509763. DOI: 10.1371/journal.pone.0133619. View

16.

Yukiura H, Kano K, Kise R, Inoue A, Aoki J . Autotaxin overexpression causes embryonic lethality and vascular defects. PLoS One. 2015; 10(5):e0126734. PMC: 4438000. DOI: 10.1371/journal.pone.0126734. View

17.

Yang Y, Mou L, Liu N, Tsao M . Autotaxin expression in non-small-cell lung cancer. Am J Respir Cell Mol Biol. 1999; 21(2):216-22. DOI: 10.1165/ajrcmb.21.2.3667. View

18.

Yung Y, Stoddard N, Chun J . LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res. 2014; 55(7):1192-214. PMC: 4076099. DOI: 10.1194/jlr.R046458. View

19.

Barbayianni E, Kaffe E, Aidinis V, Kokotos G . Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog Lipid Res. 2015; 58:76-96. DOI: 10.1016/j.plipres.2015.02.001. View

20.

Manitsopoulos N, Orfanos S, Kotanidou A, Nikitopoulou I, Siempos I, Magkou C . Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation. Respir Res. 2015; 16:24. PMC: 4336762. DOI: 10.1186/s12931-015-0173-y. View