Tuberculosis and Respiratory Diseases

  • 제68권6호
  • /
  • Pages.334-344
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  • 2010
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  • 1738-3536(pISSN)
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  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
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Moxifloxacin의 Secretory $PLA_2$억제가 올레인 산으로 유도된 호중구성 급성 폐손상에 미치는 영향

Moxifloxacin Ameliorates Oleic Acid-induced Acute Lung Injury by Modulation of Neutrophilic Oxidative Stress in Rats

  • 김병용 (대구가톨릭대학교 의과대학 생리학교실) ;
  • 이영만 (대구가톨릭대학교 의과대학 생리학교실)
  • Kim, Byung-Yong (Department of Physiology, Daegu Catholic University School of Medicine) ;
  • Lee, Young-Man (Department of Physiology, Daegu Catholic University School of Medicine)
  • 투고 : 2010.03.26
  • 심사 : 2010.05.20
  • 발행 : 2010.06.30
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초록

Background: Based on the known immunoregulatory functions of moxifloxacin on phagocytes, the therapeutic effect of moxifloxacin on oleic acid (OA)-induced acute lung injury (ALI) was investigated. Methods: Moxifloxacin (10 mg/kg) was given to male Sprague-Dawley rats that had been given oleic acid (OA, $30{\mu}L$) intravenously. Five hours after OA injection, parameters demonstrating ALI were assessed to measure the effects of moxifloxacin on acute lung injury. Results: The pathological findings of OA-induced ALI's was diminished by moxifloxacin. Through ultrastructural and $CeCl_3$ EM histochemistry, moxifloxacin was confirmed to be effective in decreasing oxidative stress in the lung as well. Indices of ALI, such as lung weight/body weight ratio, protein content in bronchoalveolar lavage fluid, and lung myeloperoxidase were decreased by moxifloxacin. In diaminobenzidine immunohistochemistry, fluorescent immunohistochemistry, and Western blotting of the lung, moxifloxacin had decreased the enhanced expression of secretory phospholipase $A_2$ ($sPLA_2$) by OA. Conclusion: We concluded that moxifloxacin was effective in lessening acute inflammatory pulmonary edema caused by OA, by inhibiting the neutrophilic respiratory burst, which was initiated by the activation of $sPLA_2$.

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참고문헌

  1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-24. https://doi.org/10.1164/ajrccm.149.3.7509706
  2. Pruzanski W, Vadas P. Phospholipase A2: a mediator between proximal and distal effectors of inflammation. Immunol Today 1991;12:143-6.
  3. Pittet JF, Mackersie RC, Martin TR, Matthay MA. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 1997;155:1187-205. https://doi.org/10.1164/ajrccm.155.4.9105054
  4. Chenevier-Gobeaux C, Simonneau C, Therond P, Bonnefont- Rousselot D, Poiraudeau S, Ekindjian OG, et al. Implication of cytosolic phospholipase A2 (cPLA2) in the regulation of human synoviocyte NADPH oxidase (Nox2) activity. Life Sci 2007;81:1050-8. https://doi.org/10.1016/j.lfs.2007.08.018
  5. Dana R, Malech HL, Levy R. The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils. Biochem J 1994;297(Pt1):217-23.
  6. Schaloske RH, Dennis EA. The phospholipase A2 superfamily and its group numbering system. Biochim Biophys Acta 2006;1761:1246-59. https://doi.org/10.1016/j.bbalip.2006.07.011
  7. Lee YM, Hybertson BM, Cho HG, Terada LS, Cho O, Repine AJ, et al. Platelet-activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally. Am J Physiol Lung Cell Mol Physiol 2000;279: L75-80.
  8. Martensson J, Jain A, Stole E, Frayer W, Auld PA, Meister A. Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress. Proc Natl Acad Sci U S A 1991;88:9360-4. https://doi.org/10.1073/pnas.88.20.9360
  9. Furue S, Kuwabara K, Mikawa K, Nishina K, Shiga M, Maekawa N, et al. Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits. Am J Respir Crit Care Med 1999;160:1292-302. https://doi.org/10.1164/ajrccm.160.4.9812042
  10. Werber S, Shalit I, Fabian I, Steuer G, Weiss T, Blau H. Moxifloxacin inhibits cytokine-induced MAP kinase and NF-kappaB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line. J Antimicrob Chemother 2005;55:293-300. https://doi.org/10.1093/jac/dkh525
  11. Weiss T, Shalit I, Blau H, Werber S, Halperin D, Levitov A, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NFkappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines. Antimicrob Agents Chemother 2004;48:1974-82. https://doi.org/10.1128/AAC.48.6.1974-1982.2004
  12. Uriarte SM, Molestina RE, Miller RD, Bernabo J, Farinati A, Eiguchi K, et al. Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alphastimulated endothelial cells. Antimicrob Agents Chemother 2004;48:2538-43. https://doi.org/10.1128/AAC.48.7.2538-2543.2004
  13. Shalit I, Horev-Azaria L, Fabian I, Blau H, Kariv N, Shechtman I, et al. Immunomodulatory and protective effects of moxifloxacin against Candida albicans-induced bronchopneumonia in mice injected with cyclophosphamide. Antimicrob Agents Chemother 2002;46: 2442-9. https://doi.org/10.1128/AAC.46.8.2442-2449.2002
  14. Shiue ST, Thrall RS. Effect of corticosteroid therapy on the acute injury and recovery stage of oleic acid induced lung injury in the rat. Exp Lung Res 1991;17: 629-38. https://doi.org/10.3109/01902149109062870
  15. Brown RE, Jarvis KL, Hyland KJ. Protein measurement using bicinchoninic acid: elimination of interfering substances. Anal Biochem 1989;180:136-9. https://doi.org/10.1016/0003-2697(89)90101-2
  16. Goldblum SE, Wu KM, Jay M. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol 1985;59:1978-85.
  17. Hobson J, Wright J, Churg A. Histochemical evidence for generation of active oxygen species on the apical surface of cigarette-smoke-exposed tracheal explants. Am J Pathol 1991;139:573-80.
  18. Matalon S, Ji HL. Oleic acid damages ion transport and promotes alveolar edema: the dark side of healthy living. Am J Respir Crit Care Med 2005;171:424-5. https://doi.org/10.1164/rccm.2411005
  19. Lee YM, Kim BY, Park YY. Role of the PLA2-activated neutrophilic oxidative stress in oleic acid-induced acute lung injury. Tuberc Respir Dis 2010;68:55-61. https://doi.org/10.4046/trd.2010.68.2.55
  20. Williams AC, Galley HF, Webster NR. The effect of moxifloxacin on release of interleukin-8 from human neutrophils. Br J Anaesth 2001;87:671-2.
  21. Zimmermann GS, Neurohr C, Villena-Hermoza H, Hatz R, Behr J. Anti-inflammatory effects of antibacterials on human Bronchial epithelial cells. Respir Res 2009;10:89. https://doi.org/10.1186/1465-9921-10-89
  22. Hand WL, Hand DL, Vasquez Y. Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes. Diabetes Res Clin Pract 2007;76:44-50. https://doi.org/10.1016/j.diabres.2006.07.015
  23. Ljungman AG, Tagesson C, Lindahl M. Endotoxin stimulates the expression of group II PLA2 in rat lung in vivo and in isolated perfused lungs. Am J Physiol 1996;270:L752-60.
  24. Arbibe L, Vial D, Rosinski-Chupin I, Havet N, Huerre M, Vargaftig BB, et al. Endotoxin induces expression of type II phospholipase A2 in macrophages during acute lung injury in guinea pigs: involvement of TNF-alpha in lipopolysaccharide-induced type II phospholipase A2 synthesis. J Immunol 1997;159:391-400.
  25. Lindbom J, Ljungman AG, Lindahl M, Tagesson C. Increased gene expression of novel cytosolic and secretory phospholipase A(2) types in human airway epithelial cells induced by tumor necrosis factor-alpha and IFN-gamma. J Interferon Cytokine Res 2002;22:947-55. https://doi.org/10.1089/10799900260286650