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Effects of SDF-1/CXCR4 on Acute Lung Injury Induced by Cardiopulmonary Bypass

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Abstract

Acute lung injury (ALI) is one of the most important complications after cardiopulmonary bypass (CPB) and the complex pathophysiology remains to be resolved incomplete. SDF-1/CXCR4 chemokine axis can chemotactically accumulate inflammatory cell to local tissue and regulate the release of inflammatory factors, and SDF-1 has a strong chemotaxis effect on neutrophils with CXCR4. Since CPB animal model was difficult to establish, there was still no report about the effect of SDF-1/CXCR4 on neutrophil chemotaxis in ALI after CPB. Here, a stable CPB rat model was constructed to clarify the role of SDF-1/CXCR4 axis in the CPB-induced ALI. Real-time quantitative PCR (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of SDF-1 and CXCR4 in lung tissues, blood, bronchoalveolar lavage (BALF), and/or isolated neutrophils. SDF-1/CXCR4 was increased after CPB, both of that were increased in blood; CXCR4 was increased in neutrophils; SDF-1/CXCR4 was also increased in BALF of CPB model. Results indicated that SDF-1/CXCR4 axis played a key role in the process of early ALI after CPB, also showed that lung injury was significantly reduce after blocking SDF-1/CXCR4 axis, suggest that CXCR4 might be a new target for ALI treatment.

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References

  1. Perl, M., J. Lomas-Neira, F. Venet, C.S. Chung, and A. Ayala. 2011. Pathogenesis of indirect (secondary) acute lung injury. Expert Review of Respiratory Medicine 5: 115–126.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Koch, C., L. Li, P. Figueroa, T. Mihaljevic, L. Svensson, and E.H. Blackstone. 2009. Transfusion and pulmonary morbidity after cardiac surgery. Annals of Thoracic Surgery 88: 1410–1418.

    Article  PubMed  Google Scholar 

  3. Vlaar, A.P., J.J. Hofstra, R.M. Determann, D.P. Veelo, F. Paulus, W. Kulik, J. Korevaar, B.A. de Mol, M.M. Koopman, L. Porcelijn, J.M. Binnekade, M.B. Vroom, M.J. Schultz, and N.P. Juffermans. 2011. The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study. Blood 117: 4218–4225.

    Article  CAS  PubMed  Google Scholar 

  4. Luehr, M., J. Bachet, F.W. Mohr, and C.D. Etz. 2014. Modern temperature management in aortic arch surgery: the dilemma of moderate hypothermia. European Journal of Cardio-Thoracic Surgery 45: 27–39.

    Article  PubMed  Google Scholar 

  5. Ng, C.S., S. Wan, A.P. Yim, and A.A. Arifi. 2002. Pulmonary dysfunction after cardiac surgery. Chest 121: 1269–1277.

    Article  PubMed  Google Scholar 

  6. Bhatia, M., R.L. Zemans, and S. Jeyaseelan. 2012. Role of chemokines in the pathogenesis of acute lung injury. American Journal of Respiratory Cell and Molecular Biology 46: 566–572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Xiang, M., and J. Fan. 2010. Pattern recognition receptor-dependent mechanisms of acute lung injury. Molecular Medicine 16: 69–82.

    Article  CAS  PubMed  Google Scholar 

  8. Kallet, R.H., and M.A. Matthay. 2013. Hyperoxic acute lung injury. Respiratory Care 58: 123–141.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Raghavendran, K., G.S. Pryhuber, P.R. Chess, B.A. Davidson, P.R. Knight, and R.H. Notter. 2008. Pharmacotherapy of acute lung injury and acute respiratory distress syndrome. Current Medicinal Chemistry 15: 1911–1924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Martin, C., P.C. Burdon, G. Bridger, J.C. Gutierrez-Ramos, T.J. Williams, and S.M. Rankin. 2003. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19: 583–593.

    Article  CAS  PubMed  Google Scholar 

  11. Furze, R.C., and S.M. Rankin. 2008. Neutrophil mobilization and clearance in the bone marrow. Immunology 125: 281–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Petty, J.M., V. Sueblinvong, C.C. Lenox, C.C. Jones, G.P. Cosgrove, C.D. Cool, P.R. Rai, K.K. Brown, D.J. Weiss, M.E. Poynter, and B.T. Suratt. 2007. Pulmonary stromal-derived factor-1 expression and effect on neutrophil recruitment during acute lung injury. Journal of Immunology 178: 8148–8157.

    Article  CAS  Google Scholar 

  13. Delano, M.J., K.M. Kelly-Scumpia, T.C. Thayer, R.D. Winfield, P.O. Scumpia, A.G. Cuenca, P.B. Harrington, K.A. O’Malley, E. Warner, S. Gabrilovich, C.E. Mathews, D. Laface, P.G. Heyworth, R. Ramphal, R.M. Strieter, L.L. Moldawer, and P.A. Efron. 2011. Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling. Journal of Immunology 187: 911–918.

    Article  CAS  Google Scholar 

  14. Zernecke, A., I. Bot, Y. Djalali-Talab, E. Shagdarsuren, K. Bidzhekov, S. Meiler, R. Krohn, A. Schober, M. Sperandio, O. Soehnlein, J. Bornemann, F. Tacke, E.A. Biessen, and C. Weber. 2008. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circulation Research 102: 209–217.

    Article  CAS  PubMed  Google Scholar 

  15. Hartl, D., S. Krauss-Etschmann, B. Koller, P.L. Hordijk, T.W. Kuijpers, F. Hoffmann, A. Hector, E. Eber, V. Marcos, I. Bittmann, O. Eickelberg, M. Griese, and D. Roos. 2008. Infiltrated neutrophils acquire novel chemokine receptor expression and chemokine responsiveness in chronic inflammatory lung diseases. Journal of Immunology 181: 8053–8067.

    Article  CAS  Google Scholar 

  16. Liu, K., L. Shen, J. Wang, G. Dong, H. Wu, H. Shao, and H. Jing. 2012. The preventative role of curcumin on the lung inflammatory response induced by cardiopulmonary bypass in rats. Journal of Surgical Research 174: 73–82.

    Article  CAS  PubMed  Google Scholar 

  17. Liu, K., H.L. Chen, H. Huang, H. Jing, G.H. Dong, H.W. Wu, and Q.S. You. 2012. Curcumin attenuates cardiopulmonary bypass-induced lung oxidative damage in rats. Journal of Cardiovascular Pharmacology and Therapeutics 17: 395–402.

    Article  CAS  PubMed  Google Scholar 

  18. Lukacs, N.W., A. Berlin, D. Schols, R.T. Skerlj, and G.J. Bridger. 2002. AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway hyperreactivity. American Journal of Pathology 160: 1353–1360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  20. Heikkinen, L.O., and K.V. Alakulju. 2009. Abdominal complications following cardiopulmonary bypass in open-heart surgery. Scandinavian Journal of Thoracic and Cardiovascular Surgery 95: 1–7.

    Google Scholar 

  21. Dhein, S., M. Grassl, M. Gerdom, M. Vollroth, F. Bakhtiary, S. von Salisch, K. Krämer, A. Sobiraj, M. Kostelka, F.W. Mohr, and A. Salameh. 2015. Organ-protective effects on the liver and kidney by minocycline in small piglets undergoing cardiopulonary bypass. Naunyn-Schmiedeberg’s Archives of Pharmacology 388: 663–676.

    Article  CAS  PubMed  Google Scholar 

  22. Du, S., J. Ai, X. Zeng, J. Wan, X. Wu, and J. He. 2016. Plasma level of advanced oxidation protein products as a novel biomarker of acute lung injury following cardiac surgery. Springerplus 5: 231.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Senay, S., F. Toraman, S. Gunaydin, M. Kilercik, H. Karabulut, and C. Alhan. 2009. The impact of allogenic red cell transfusion and coated bypass circuit on the inflammatory response during cardiopulmonary bypass: a randomized study. Interactive Cardiovascular and Thoracic Surgery 8: 93–99.

    Article  PubMed  Google Scholar 

  24. Melley, D.D., T.W. Evans, and G.J. Quinlan. 2005. Redox regulation of neutrophil apoptosis and the systemic inflammatory response syndrome. Clinical Science (London) 108: 413–424.

    Article  CAS  Google Scholar 

  25. Fujishima, S., H. Morisaki, A. Ishizaka, Y. Kotake, M. Miyaki, K. Yoh, K. Sekine, J. Sasaki, S. Tasaka, N. Hasegawa, Y. Kawai, J. Takeda, and N. Aikawa. 2008. Neutrophil elastase and systemic inflammatory response syndrome in the initiation and development of acute lung injury among critically ill patients. Biomedicine and Pharmacotherapy 62: 333–338.

    Article  CAS  PubMed  Google Scholar 

  26. Yamada, M., H. Kubo, S. Kobayashi, K. Ishizawa, M. He, T. Suzuki, N. Fujino, H. Kunishima, M. Hatta, K. Nishimaki, T. Aoyagi, K. Tokuda, M. Kitagawa, H. Yano, H. Tamamura, N. Fujii, and M. Kaku. 2011. The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury. Cellular and Molecular Immunology 8: 305–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by grants from Six Talent Peaks Project in Jiangsu Province, China (no. 2014-YY-006), the Postdoctoral Science Foundation of China (no. 2013M541705), the Postdoctoral Research Foundation of Jiangsu Province, China (no. 1301072C), and the Science Foundation of Nantong City, Jiangsu Province, China (nos. HS2012025 and MS32015016).

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    Authors and Affiliations

    1. Department of Cardiothoracic Surgery, The Third People’s Hospital of Nantong, Nantong, Jiangsu, 226001, People’s Republic of China

      Hai Shi & Rujian Lu

    2. Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China

      Shuo Wang & Honglin Chen

    3. Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China

      Fei Wang & Kun Liu

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    1. Hai Shi
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    Correspondence to Fei Wang or Kun Liu.

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    All procedures of animal treatments were in accordance with the guidelines for experimental animals approved by the Animal Care and Use Committee of Nantong University (China).

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    The authors declare that they have no conflict of interest.

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    Hai Shi and Rujian Lu contributed equally to this work.

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    Shi, H., Lu, R., Wang, S. et al. Effects of SDF-1/CXCR4 on Acute Lung Injury Induced by Cardiopulmonary Bypass. Inflammation 40, 937–945 (2017). https://doi.org/10.1007/s10753-017-0538-0

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    • DOI: https://doi.org/10.1007/s10753-017-0538-0

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