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Inflammation Research

Erschienen in:

01.08.2012 | Original Research Paper

Pretreatment with anti-flagellin serum delays acute lung injury in rats with sepsis

verfasst von: Ming-Dong Hu, Yu Yang, Chang-Xi Zhou, Qi Li, Wang Yi, Gui-Sheng Qian, Mei Mao, Jian-Cheng Xu

Erschienen in: Inflammation Research | Ausgabe 8/2012

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Abstract

Objective

This study examined the reduction of sepsis-induced ALI by inhibition of flagellin-stimulated TLR5 signaling.

Methods

Rats were randomly divided into three groups: one group served as the sham-operated group (control group), and the other two groups received the induction of sepsis (sepsis and treatment groups). The treatment group was injected with anti-flagellin serum before induction of sepsis. At 2, 4, 6, 12, 24, and 48 h following induction of sepsis (six time-point subgroups, n = 10 per subgroup), arterial PaO₂, wet/dry (W/D) lung weight ratios, levels of serum and BALF flagellin and TNF-α, pulmonary pathological alterations, and TLR5 mRNA expression in the lungs were examined.

Results

Compared to sham-operated rats, septic rats had: increased levels of serum and BALF flagellin at 6, 12, 24, and 48 h; reduced arterial PaO₂; elevated W/D lung weight ratio; increased serum and BALF TNF-α levels; and up-regulated TLR5 mRNA expression at 12, 24, and 48 h (P < 0.01). Pretreatment with anti-flagellin serum, however, significantly inhibited sepsis-associated declines in arterial PaO₂, increased W/D lung weight ratios, elevated serum and BALF TNF-α levels, and up-regulated TLR5 mRNA expression at 24 and 48 h (P < 0.01).

Conclusion

Neutralizing the actions of circulating flagellin with anti-flagellin serum delayed the development of ALI in rats with sepsis.

Zambon M, Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008;133(5):1120–7.PubMedCrossRef

Rojas M, Woods CR, Mora AL, Xu J, Brigham KL. Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses. Am J Physiol Lung Cell Mol Physiol. 2005;288(2):L333–41.PubMedCrossRef

Asti C, Ruggieri V, Porzio S, Chiusaroli R, Melillo G, Caselli GF. Lipopolysaccharide-induced lung injury in mice. I. Concomitant evaluation of inflammatory cells and haemorrhagic lung damage. Pulm Pharmacol Ther. 2000;13(2):61–9.PubMedCrossRef

Wiener-Kronish JP, Albertine KH, Matthay MA. Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. J Clin Invest. 1991;88(3):864–75.PubMedCrossRef

Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 2007;4(9):e269.PubMedCrossRef

Bone RC, Balk RA, Fein AM, Perl TM, Wenzel RP, Reines HD, Quenzer RW, Iberti TJ, Macintyre N, Schein RM. A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. Crit Care Med. 1995;23(6):994–1006.PubMedCrossRef

Zhou CX, Xu JC, Hu MD, Yang Y. Significance of changes in serum and BALF flagellin levels in septic rats with acute lung injury. Chin J Intern Med. 2006;45(10):842–3.

Eaves-Pyles T, Murthy K, Liaudet L, Virág L, Ross G, Soriano FG, Szabó C, Salzman AL. Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction. J Immunol. 2001;166(2):1248–60.PubMed

Liaudet L, Szabó C, Evgenov OV, Murthy KG, Pacher P, Virág L, Mabley JG, Marton A, Soriano FG, Kirov MY, Bjertnaes LJ, Salzman AL. Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis. Shock. 2003;19(2):131–7.PubMedCrossRef

10.

Liaudet L, Murthy KG, Mabley JG, Pacher P, Soriano FG, Salzman AL, Szabό C. Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar Muenchen flagellin and serovar enteritidis lipopolysaccharide. Infect Immun. 2002;70(1):192–8.PubMedCrossRef

11.

Rolli J, Loukili N, Levrand S, Rosenblatt-Velin N, Rignault-Clerc S, Waeber B, Feihl F, Pacher P, Liaudet L. Bacterial flagellin elicits widespread innate immune defense mechanisms, apoptotic signaling, and a sepsis-like systemic inflammatory response in mice. Crit Care. 2010;14(4):R160.PubMedCrossRef

12.

Hawn TR, Berrington WR, Smith IA, Uematsu S, Akira S, Aderem A, Smith KD, Skerrett SJ. Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila. J Immunol. 2007;179(10):6981–7.PubMed

13.

Liaudet L, Deb A, Pacher P, Mabley JG, Murthy KG, Salzman AL, Szabo C. The flagellin-TLR5 axis: rherapeutic opportunities. Drug News Perspect. 2002;15(7):397–409.PubMedCrossRef

14.

Hu MD, Xu JC, Feng YK, Zhou CX, Gong CM. Isolation and purification of flagellin from Salmonella paratyphi A and preparation of its specific antiserum. Acta Academiae Medicinae Militaris Tertiae. 2005;27(7):607–9.

15.

Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2008;295(3):L379–99.PubMedCrossRef

16.

Daniel R, Markus SH, Michael AF, Peter AW. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009;4(1):31–6.

17.

You ZC, Shi Z, Gao QJ, Zhou K, Li X, Lu YB. The study of preventive and therapeutic effects of edaravone against paraquat-induced acute lung injury. Chongqing Med J. 2008;37(22):2517–9.

18.

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

19.

Perl M, Lomas-Neira J, Chung CS, Ayala A. Epithelial cell apoptosis and neutrophil recruitment in acute lung injury-a unifying hypothesis? What we have learned from small interfering RNAs. Mol Med. 2008;14(7–8):465–75.PubMed

20.

Szabó C. Role of flagellin in the pathogenesis of shock and acute respiratory distress syndrome: therapeutic opportunities. Crit Care Med. 2003;31(1):S39–45.PubMedCrossRef

21.

Hu MD, Xu JC, Xhou CX, Yang Y. A study of acute lung injury in different time phases after injection of flagellin via vena caudalis. Chin J Crit Care Med. 2008;28(7):614–7.

22.

Barnea Y, Carmeli Y, Neville LF, Kahel-Reifer H, Eren R, Dagan S, Navon-Venezia S. Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model. Burns. 2009;35(3):390–6.PubMedCrossRef

23.

O’Neill LA, Greene C. Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol. 1998;63(6):650–7.PubMed

24.

Muir A, et al. Toll-like receptors in normal and cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol. 2004;30(6):777–83.PubMedCrossRef

25.

Li JM, Shah AM. Endothelial cell super-oxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol. 2004;287(5):R1014–30.PubMedCrossRef

26.

Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6823):1099–103.PubMedCrossRef

27.

Bambou JC, Giraud A, Menard S, Begue B, Rakotobe S, Heyman M, Taddei F, Cerf-Bensussan N, Gaboriau-Routhiau V. In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain. J Biol Chem. 2004;279(41):42984–92.PubMedCrossRef

Titel: Pretreatment with anti-flagellin serum delays acute lung injury in rats with sepsis
verfasst von: Ming-Dong Hu
Yu Yang
Chang-Xi Zhou
Qi Li
Wang Yi
Gui-Sheng Qian
Mei Mao
Jian-Cheng Xu
Publikationsdatum: 01.08.2012
Verlag: SP Birkhäuser Verlag Basel
Erschienen in: Inflammation Research / Ausgabe 8/2012
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-012-0475-1

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