생명과학회지 (Journal of Life Science)

  • 제21권8호
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  • Pages.1100-1108
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  • 2011
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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흰쥐에서 내독소로 유도된 급성 폐손상에서 moxofloxacin의 개선효과

Ameliorating Effects of Moxifloxacin on Endotoxin-Induced Acute Lung Injury in Rats

  • 이영만 (대구가톨릭대학교 의과대학 생리학교실) ;
  • 최휘건 (대구가톨릭대학교 의과대학 생화학교실)
  • Lee, Young-Man (Department of Physiology, Daegu Catholic University) ;
  • Chae, Whi-Gun (Department of Biochemistry, School of Medicine, Daegu Catholic University)
  • 투고 : 2011.07.13
  • 심사 : 2011.07.29
  • 발행 : 2011.08.30
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초록

흰쥐에서 내독소로 유도된 급성 폐손상에서 moxifloxacin의 효과를 형태학적으로 호중구의 폐장 내 침윤 및 세포질형 포스포리파아제(cytosolic phospholipase A2) 발현과 관련하여 알아보았다. 내독소는 잘 알려진대로 흰쥐에서 급성 폐손상을 유발하였고 이때 폐장 내의 호중구의 침윤 및 폐장 및 호중구에서의 세포질형 포스포리파아제의 발현이 증가하였고, 또한 염증성 사이토카인의 일종인 종양괴사성인자(tumor necrosis factor)의 발현도 증가하였다. 전자현미경을 이용한 산소기 생성의 검사에서도 내독소에 의하여 산소기의 생성이 폐장 내에 증가한 사실을 확인하였고, 산화성 스트레스에 유발되는 제2형 폐포세포에서의 층상체의 변화도 관찰하였다. 면역변환효과가 있다고 알려진 moxifloxacin은 이러한 변화들을 억제하고 형태학적으로 내독소에 의한 급성 폐손상을 현저히 감소시켰다.

The immunomodulating effects of moxifloxacin seem to be effective in downregulating inflammatory reactions. This presumed effect was tested in endotoxin (ETX)-induced acute lung injury (ALI) in rats. After moxifloxacin treatment (10 mg/kg) of ETX-given rats, lung myeloperoxidase (MPO) activity, bronchoalveolar-lavage (BAL) protein, and the number of neutrophils in the BAL cells were measured. Light and electron microscopic structures were also examined. Electron microscopic $CeCl_3$ histochemistry for the detection of hydrogen peroxide in the lungs and immunohistochemistry of cytosolic phospholipase A2 (cPLA2) in the lung tissues and BAL cells were performed. To examine the expression of TNF${\alpha}$ in the lungs, western blotting was carried out with the lung tissues. ETX had accumulated neutrophils in the lungs, which was followed by lung leak. Oxidative stress occurred, and increased expression of cPLA2 in the lung tissues and BAL cells was observed in the ETX-given rats. Simultaneously, the expression of TNF${\alpha}$ was enhanced by ETX. Moxifloxacin, however, decreased all these parameters, indicating that ALI may have been ameliorated. Moxifloxacin appears to ameliorate ETX-induced ALI partially through the suppression of cPLA2 in the lungs of rats.

키워드

참고문헌

  1. Bhatia, M. and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J. Pathol. 202, 145-156. https://doi.org/10.1002/path.1491
  2. Brown, R. E., J. L. Jarvis, and K. J. Hyland. 1989. Protein measurement using bicinchoninic acid: elimination of interfering substance. Anal. Biochem. 180, 136-139. https://doi.org/10.1016/0003-2697(89)90101-2
  3. Dallhof, A. and I. Shalit. 2003. Immunoregulatory effects of quinolones. Lancet Infec. Dis. 3, 359-371. https://doi.org/10.1016/S1473-3099(03)00658-3
  4. Delclaux, C., S. Rezaiguia-Delclaux, C. Delacourt, C. Brun-Buisson, C. Lafuma, and A. Harf. 1997. Alveolar neutrophils in endotoxin-induced acute lung injury in rats. Am. J. Physiol. 273, L104-112.
  5. Goldblum, S. E., K. E. Wu, and M. Jay. 1985. Lung myeloperoxidase as a measurement of leukostasis in rabbits. J. Appl. Physiol. 119, 101-110.
  6. Hite, R. D., M. C. Seeds, R. B. Jacinto, R. Balasubramania, and M. Waite. 1998. Hydrolysis of surfactant associated phosphatidylcholine by mammalian secretory phospholipase A2. Am. J. Physiol. 275, L740-747.
  7. Holm, B. A., L. Keicher, M. A. Liu, J. Sokolowski, and G. Enhorning. 1991. Inhibition of pulmonary surfactant function by phospholipases. J. Appl. Physiol. 71, 317-321.
  8. Huang, H., C. Shieh, K. W. Yu, K. Cheng, and C. Chen. 2008. Comparing the protective effects of ciprofloxacin, moxifloxacin and levofloxacin in mice with lipopolysaccharide- induced acute lung injuries. Repirology 13, 47-52. https://doi.org/10.1111/j.1440-1843.2007.01192.x
  9. Hybertson, B. M., Y. M. Lee, H. G. Cho, O. J. Cho, and J. E. Repine. 2000. Alveolar type II cell abnormalities and peroxide formation in lungs of rats given IL-1 intratracheally. Inflammation 24, 289-303. https://doi.org/10.1023/A:1007092529261
  10. Kitsioluli, E., G. Nakos, and M. E. Lekka. 2009. Phospholipase A2 subclasses in acute respiratory distress syndrome. Biochim. Biophys. Acta 1792, 941-53. https://doi.org/10.1016/j.bbadis.2009.06.007
  11. Lekka, M. E., S. Liokatis, C. Nathanail, V. Galani, and G. Nakos. 2004. The impact of intravenous fat emulsion administration in the acute lung injury. Am. J. Respire. Crit. Care Med. 169, 638-644. https://doi.org/10.1164/rccm.200305-620OC
  12. Leslie, C. C. 1997. Properties and regulation of cytosolic phospholipase A2. J. Biol. Chem. 272, 709-712. https://doi.org/10.1074/jbc.272.2.709
  13. Levy, R., R. Dana, I. Hazan, G. Weber, and R. Smoliakov. 2009. Elevated cytosolic phospholipase A2 expression and activity in human neutrophils during sepsis. Blood 95, 660-665.
  14. Levy, R. 2006. The role of phospholipase A2-alfa in regulation of phagocytic functions. Biochim. Biophys. Acta 1761, 1323-1334. https://doi.org/10.1016/j.bbalip.2006.09.004
  15. Martensson, J., A. Jain, W. Frayer, and A. Meister. 1989. Glutathione metabolism in the lung: inhibition of its synthesis leads to lamellar body and mitochondrial defects. Proc. Natl. Acad. Sci. 86, 5296-5300. https://doi.org/10.1073/pnas.86.14.5296
  16. Matthay, M. A. and R. L. Zemans. 2011. The acute respiratory distress syndrome: Pathogenesis and Treatment. Ann. Rev. Pathol. 6, 147-163. https://doi.org/10.1146/annurev-pathol-011110-130158
  17. Mendez, J. L. and R. D. Hubmayr. 2005. New insight into the pathology of acute respiratory failure. Curr. Opin. Crit. Care 11, 29-36 https://doi.org/10.1097/00075198-200502000-00005
  18. Mueller, J. M., H. W. Loems Ziegler-Heitbrock, and P. A. Baeuerle. 1993. Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiol. 187, 233-256. https://doi.org/10.1016/S0171-2985(11)80342-6
  19. Nagase, T., N. Uozumi, T. Aoki-Nagase, K. Terawaki, and S. Ishii. 2003. A potent inhibitor of cytosolic phospholipase A2, arachidonyl trifluoroethyl ketone, attenuates LPS-induced lung injury in mice. Am. J. Lung Cell Mol. Physiol. 234, L720-726.
  20. Nagase, T., N. Uozumi, S. Ishii, K. Kume, and T. Izumi. 2000. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. Nature Immunol. 1, 42-46. https://doi.org/10.1038/76897
  21. Pittet, J. F., R. C. Mackersie, T. R. Martin, and M. A. Matthay. 1997. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am. J. Respir. Crit. Care Med. 155, 1187-1205. https://doi.org/10.1164/ajrccm.155.4.9105054
  22. Shalit, I., D. Halperin, D. Haite, A. Levitov, and J. Romano. 2006. Anti-inflammatory effects of moxofloxacin on IL-8, IL-1$\beta$ and TNF$\alpha$ secretion and $NF{\kappa}B$ and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus. J. Antimicr. Chemother. 57, 230-235. https://doi.org/10.1093/jac/dki441
  23. Sorbo, D. and A. S. Slutsky. 2011. Acute respiratory distress syndrome and multiple organ failure. Curr. Opin. Crit. Care 17, 1-6. https://doi.org/10.1097/MCC.0b013e3283427295
  24. Suter, P. M., E. Suter, P, Girardin, P, Roux-Lombard, E. Grau, and J. Dayer. 1992. High bronchoalveolar level of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after traumatic shock or sepsis. Am. Rev. Respir. Dis. 145, 1016-1022. https://doi.org/10.1164/ajrccm/145.5.1016
  25. Uriarte, S. M., R. E. Molestina, R. D. Miller, J. Bernabo, and A. Farinati. 2004. Effects of fluoroquinolones on migration of human phagocytes through Chlamydia pneumoniae- infected and tumor necrosis factor alpha-stimulated endothelial cells. Antimicr. Agent Chemother. 48, 2538-2543. https://doi.org/10.1128/AAC.48.7.2538-2543.2004
  26. Warren, J. S., R. G. Kunkel, R. H. Simon, K. J. Johnson, and P. A. Ward. 1989. Ultrastructural cytochemical analysis of oxygen radical mediated immunoglobulinA immune complex induced lung injury in rat. Lab. Invest. 60, 651-658.
  27. Warren, L. L. and G. P. Downey. 2001. Neutrophil activation and acute lung injury. Curr. Opin. Crit. Care 7, 1-7. https://doi.org/10.1097/00075198-200102000-00001