바로가기메뉴

본문 바로가기 주메뉴 바로가기

Tuberculosis & Respiratory Diseases

Article Contents

Prev Next
e-Submission

Vol.71 No.2
Citation Share

A Study on the Mechanism of Immunomodulating Effects of Moxifloxacin in Oleic Acid-Induced Acute Lung Injury

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2011, v.71 no.2, pp.97-105
(Catholic University of Daegu)
(2011). A Study on the Mechanism of Immunomodulating Effects of Moxifloxacin in Oleic Acid-Induced Acute Lung Injury. Tuberculosis & Respiratory Diseases, 71(2), 97-105.
  • Downloaded
  • Viewed
PDF Download

Abstract

Background: It was hypothesized that the immunomodulating effects of moxifloxacin contribute to ameliorate oleic acid (OA)-induced acute lung injury (ALI) by suppression of cytosolic phospholipase A2 (cPLA2). This was based on observations from experiments on rats associated with neutrophilic respiratory burst, cPLA2 activity, and expressions of cPLA2, TNFα, and COX-II in the lung. Methods: ALI was induced by intravenous injection of OA in male Sprague-Dawley rats. Five hours after OA injection, protein content in bronchoalveolar lavage (BAL), lung myeloperoxidase (MPO) activity, and numbers of BAL neutrophils were measured. As an index of oxidative stress-induced lung injury, the content of malondialdehyde (MDA) in lung tissues was also determined. Lung histology, immunohistochemistry and determination of activity of cPLA2 in lung tissues were carried out. In addition, Western blotting of TNFα and COX-II in lung tissues was performed. Results: The accumulation of neutrophils in the lungs was observed after OA injection. BAL protein was increased along with neutrophilic infiltration and migration by OA. Moxifloxacin decreased all of these parameters of ALI and ameliorated ALI histologically. The increased malondialdehyde (MDA) in the lung by OA was also decreased by moxifloxacin. Moxifloxacin not only suppressed cPLA2 expression in the lungs and neutrophils but also decreased cPLA2 activity in lung tissues of rats given OA. The enhanced expressions of TNFα and COX-2 in the lung tissues of rats given OA were also suppressed by moxifloxacin. Conclusion: Moxifloxacin inhibited cPLA2 and down-regulated TNFα and COX-2 in the lungs of rats given OA, which resulted in the attenuation of inflammatory lung injury.

keywords
Moxifloxacin, Oleic Acid, Neutrophils, Acute Lung Injury, Moxifloxacin, Oleic Acid, Neutrophils, Acute Lung Injury

Reference

1.

1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967;2:319-23.

2.

2. Kim DK, Fukuda T, Thompson BT, Cockrill B, Hales C, Bonventre JV. Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am J Physiol 1995;269(1 Pt 1):L109-18.

3.

3. Magrioti V, Kokotos G. Phospholipase A2 inhibitors as potential therapeutic agents for the treatment of inflammatory diseases. Expert Opin Ther Pat 2010;20:1- 18.

4.

4. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000;342:1334-49.

5.

5. Sherr S, Montemurno R, Raffer P. Lipids of recovered pulmonary fat emboli following trauma. J Trauma 1974;14:242-6.

6.

6. Julien M, Hoeffel JM, Flick MR. Oleic acid lung injury in sheep. J Appl Physiol 1986;60:433-40.

7.

7. Karagiorga G, Nakos G, Galiatsou E, Lekka ME. Biochemical parameters of bronchoalveolar lavage fluid in fat embolism. Intensive Care Med 2006;32:116-23.

8.

8. Nagase T, Uozumi N, Ishii S, Kume K, Izumi T, Ouchi Y, et al. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. Nat Immunol 2000;1:42-6.

9.

9. Leslie CC. Properties and regulation of cytosolic phospholipase A2. J Biol Chem 1997;272:16709-12.

10.

10. Ishitsuka Y, Moriuchi H, Hatamoto K, Yang C, Takase J, Golbidi S, et al. Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs. J Pharm Pharmacol 2004;56:513-20.

11.

11. Ito K, Mizutani A, Kira S, Mori M, Iwasaka H, Noguchi T. Effect of Ulinastatin, a human urinary trypsin inhibitor, on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes. Injury 2005;36:387-94.

12.

12. Dalhoff A, Shalit I. Immunomodulatory effects of quinolones. Lancet Infect Dis 2003;3:359-71.

13.

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.

14.

14. Derks CM, Jacobovitz-Derks D. Embolic pneumopathy induced by oleic acid. A systematic morphologic study. Am J Pathol 1977;87:143-58.

15.

15. Brown RE, Jarvis KL, Hyland KJ. Protein measurement using bicinchoninic acid: elimination of interfering substances. Anal Biochem 1989;180:136-9.

16.

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.

17. Carraway MS, Piantadosi CA, Jenkinson CP, Huang YC. Differential expression of arginase and iNOS in the lung in sepsis. Exp Lung Res 1998;24:253-68.

18.

18. Katsumata M, Gupta C, Goldman AS. A rapid assay for activity of phospholipase A2 using radioactive substrate. Anal Biochem 1986;154:676-81.

19.

19. Fischer S, Adam D. Effects of moxifloxacin on neutrophil phagocytosis, burst production, and killing as determined by a whole-blood cytofluorometric method. Antimicrob Agents Chemother 2001;45:2668-9.

20.

20. Donnarumma G, Paoletti I, Buommino E, Iovene MR, Tudisco L, Cozza V, et al. Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line (A549) stimulated with lipopolysaccharide. Peptides 2007;28:2286-92.

21.

21. 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.

22.

22. Levy R. The role of cytosolic phospholipase A2-alfa in regulation of phagocytic functions. Biochim Biophys Acta 2006;1761:1323-34.

23.

23. Shalit I, Halperin D, Haite D, Levitov A, Romano J, Osherov N, et al. Anti-inflammatory effects of moxifloxacin on IL-8, IL-1beta and TNF-alpha secretion and NFkappaB and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus. J Antimicrob Chemother 2006;57:230-5.

24.

24. Kwon YS, Hyun DS, Lee YM. Cytosolic phospholipase A2 activity in neutrophilic oxidative stress of platelet- activating factor-induced acute lung injury. Tuberc Respir Dis 2007;63:497-506.

Tuberculosis & Respiratory Diseases

e-Submission OA Policy