생명과학회지 (Journal of Life Science)

  • 제20권4호
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  • Pages.474-480
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  • 2010
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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Interleukin-1으로 유도된 급성폐손상에서 rutin의 효과

Rutin Ameliorates Neutrophilic Oxidative Stress-Induced Acute Lung Injury by Intratracheal IL-1 Insufflation in Rats

  • 권성철 (대구가톨릭대학교 의과대학 생리학교실) ;
  • 박윤엽 (대구가톨릭대학교 의과대학 생리학교실) ;
  • 이영만 (대구가톨릭대학교 의과대학 생리학교실)
  • Kwon, Sung-Chul (Department of Physiology, School of Medicine, Catholic University of Daegu) ;
  • Park, Yoon-Yub (Department of Physiology, School of Medicine, Catholic University of Daegu) ;
  • Lee, Young-Man (Department of Physiology, School of Medicine, Catholic University of Daegu)
  • 투고 : 2010.01.11
  • 심사 : 2010.03.29
  • 발행 : 2010.04.30
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초록

흰쥐에서 Interleukin-1 (IL-1)으로 유도된 급성폐손상에서의 group II phospholipase $A_2$ ($PLA_2$) 억제제인 rutin의 효과를 알아보기 위하여 본 연구를 시행하였다. Rutin은 IL-1에 의해 증가한 폐장내의 myeloperoxidase의 활성도를 감소시키지는 못하였으나 폐포세척액 내의 호중구의 수 및 모세혈관의 손상지표로 알려져 있는 폐장 모세혈관에서의 단백질 누출양을 감소시켰다. 동시에 rutin은 IL-1에 의하여 증가한 폐장의 염증조절효소인 $PLA_2$의 활성도를 감소시키고 결과적으로 호중구에서의 산소기의 생성을 감소시켰다. Rutin 뿐만 아니라 manoalide, scalaradial 같은 group II $PLA_2$의 억제제도 호중구의 respiratory burst를 감소시킴을 확인하였다. IL-1에 의하여 증가한 폐포세척액 내에서의 cytokine induced neutrophil chemoattractant의 농도는 rutin에 의해 영향을 받지 않았다. 형태학적으로는 IL-1에 의한 폐장조직에서의 산소기의 형성이 관찰되었고 rutin은 이러한 산소기의 생성을 현저히 감소시켰다. 이러한 결과로 미루어 group II $PLA_2$ 억제제인 rutin은 호중구에서의 활성 산소기의 생성을 효과적으로 억제함으로써 IL-1에 의한 급성폐손상의 감소를 가져 오는 것으로 결론지을 수 있다.

Rutin, a group II phospholipase $A_2$ ($PLA_2$) inhibitor, was tested on interleukin-1 (IL-1) induced acute lung injury (ALI) in male Sprague-Dawley rats. Rutin did not alter the increased lung myeloperoxidase activity by IL-1. However, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and IL-1 induced lung leak were decreased by rutin (p<0.001). Simultaneously, rutin decreased lung $PLA_2$ activity, which was increased by IL-1 (p<0.001). The reduction of neutrophilic respiratory burst by the inhibition of $PLA_2$ was confirmed by group II $PLA_2$ inhibitors such as rutin, manoalide and scalaradial. The increased level of cytokine-induced neutrophilic chemoattractant (CINC) in BALF by IL-1 was not affected by rutin. Ultrastructural changes of ALI and increased generation of free radicals in the lung by IL-1 were found, and rutin ameliorated these pathological findings. Taken together, rutin seems to be effective in decreasing IL-1 induced ALI through inhibition of group II $PLA_2$.

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참고문헌

  1. Anderson, B. O., J. M. Brown, and A. H. Harken. 1991. Mechanisms of neutrophil-mediated tissue injury. J. Surg. Res. 51, 170-179. https://doi.org/10.1016/0022-4804(91)90090-9
  2. Botha, A. J., F. A. Moore, E. E. Moore, B. Fontes, A. Banerjee, and V. M. Peterson. 1995. Postinjury neutrophil priming and activation state: therapeutic challenges. Shock 3, 537-566.
  3. Bouriche, H., P. Salavei, J. Lessig, and J. Arnhold. 2007. Differential effects of flavonoids on inactivation of alpha-1-antitrypsin induced hypohalous acids and the myeloperoxidase-hydrogen peroxide-halide system. Arch. Biochem. Biophys. 459, 137-142. https://doi.org/10.1016/j.abb.2006.10.030
  4. Brown, R. E., K. 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
  5. Burke, J. E. and E. A. Dennis. 2009. Phospholipase A2 structure/function, mechanism and signaling. J. Lipid Res. 50, S237-S242 https://doi.org/10.1194/jlr.R800033-JLR200
  6. Dana, R., T. L. Leto, H. L. Malech, and R. Levy. 1998. Essential requirement of cytosolic phospholipase A2 in the activation of the NADPH oxidase. J. Biol. Chem. 273, 441-445. https://doi.org/10.1074/jbc.273.1.441
  7. Goldblum, S. E., K. M. Wu, and M. Jay. 1985. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J. Appl. Physiol. 59, 1978-1985.
  8. Haslett, C., L. A. Guthrie, M. M. Kopaniak, R. B. Johnston Jr., and P. M. Henson. 1985. Modulation of multiple neutrophil function by preparative methods or trace concentration of bacterial lipopolysaccharides. Am. J. Pathol. 119, 101-110.
  9. Karnovsky, M. J. 1994. Robert Feugen Lecture 1994. Cytochemistry and reactive oxygen species: a retrospective. Histochemistry 102, 15-27. https://doi.org/10.1007/BF00271045
  10. Katsumata, M., C. Gupta, and A. S. Goldman. 1986. Rapid assay for activity of phospholipase A2 using radioactive substrate. Anal. Biochem. 139, 573-380.
  11. Kim, F. J., E. E. Moore, F. A. Moore, W. L. Biffle, B. Fontes, and A. Banerjee. 1995. Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. J. Surg. Res. 58, 636-640. https://doi.org/10.1006/jsre.1995.1100
  12. Koh, Y., B. M. Hybertson, E. K. Jepson, O. J. Cho, and J. E. Repine. 1995. Cytokine-induced neutrophil chemoattractant is necessary for interleukin-1 induced lung leak in rats. J. Appl. Physiol. 79, 472-478.
  13. Lee, Y. M., B. M. Hybertson, H. G. Cho, and J. E. Repine. 2002. Platelet-activating factor (PAF) induces lung inflammation and leak in rats: hydrogen peroxide production along neutrophil-lung endothelial surfaces. J. Lab. Clin. Med. 140, 312-319. https://doi.org/10.1067/mlc.2002.128181
  14. Lee, Y. M., B. M. Hybertson, L. S. Terada, A. J. Repine, H. G. Cho, and J. E. Repine. 1997. Mepacrine decreases lung leak in rats given interleukin-1 intratracheally. Am. J. Respir. Crit. Care Med. 155, 1624-1628. https://doi.org/10.1164/ajrccm.155.5.9154867
  15. Leff, J. A., J. W. Baer, M. E. Bodman, J. M. Kirkman, P. F. Shanley, L. M. Patton, C. J. Beehler, J. M. McCord, and R. E. Repine. 1993. Interleukin-1 induced neutrophil accumulation and oxygen metabolite-mediated lung leak in rats. Am. J. Physiol. 265, L501-506.
  16. 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. USA 86, 5296-5300. https://doi.org/10.1073/pnas.86.14.5296
  17. Pruzanski, W. and P. Vadas. 1991. Phospholipase A2-a mediator between proximal and distal effectors of inflammation. Immunol. Today 12, 143-146.
  18. Repine, J. E. 1992. Scientific perspectives on acute respiratory syndrome. Lancet 339, 466-469. https://doi.org/10.1016/0140-6736(92)91067-I
  19. Schaloske, R. H. and E. A. Dennis. 2006. Phospholipase A2 superfamily and its group numbering system. Biochim. Biophys. Acta. 1761, 1246-1259. https://doi.org/10.1016/j.bbalip.2006.07.011
  20. Schuster, D. P. and M. H. Kollef. 1996. Acute respiratory distress syndrome. Dis. Mon. 42, 270-326. https://doi.org/10.1016/S0011-5029(96)90016-4
  21. Wittwer, A. J., L. S. Carr, J. Zagorski, G. J. Dolecki, B. A. Grippes, and J. E. De Larco. 1993. High level of expression of cytokine-induced neutrophil chemoattractant (CINC) by metastatic cell line: purification and production of blocking antibodies. J. Cell Physiol. 156, 421-427. https://doi.org/10.1002/jcp.1041560226
  22. Zemans, R. L., S. P. Colgan, and G. P. Downey. 2009. Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am. J. Respir. Cell Mol. Biol. 40, 519-535. https://doi.org/10.1165/rcmb.2008-0348TR