Skip to main content

Effects of S-Nitroso-N-Acetyl-Penicillamine (SNAP) on Inflammation, Lung Tissue Apoptosis and iNOS Activity in a Rabbit Model of Acute Lung Injury

  • Chapter
  • First Online:
Pulmonary Infection and Inflammation

Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 935))

Abstract

Acute lung injury is characterized by lung edema, surfactant dysfunction, and inflammation. The main goal of our study was to evaluate effects of S-nitroso-N-acetyl-penicillamine (SNAP) on migration of cells into the lung and their activation, inducible NO synthase (iNOS) activity, and apoptosis in experimental acute lung injury (ALI) in rabbits. ALI was induced by repetitive lung lavage with saline. The animals were divided into the following groups: (1) ALI without therapy, (2) lung injury treated with SNAP (ALI + SNAP), and (3) healthy animals (Control). After 5 h of ventilation, total and differential counts of cells in the bronchoalveolar lavage fluid (BALF) were assessed. Concentrations of interleukins (IL)-1ß, IL-6, and IL-8, endogenous secretory receptor for advanced glycation endproducts (esRAGE), sphingosine-1-phosphate receptor (S1PR)3, caspase-3, and mRNA expression of inducible NO synthase (iNOS) in lung tissue and nitrite/nitrate in plasma were analyzed. In the right lung, apoptotic cells were evaluated by TUNEL assay. In the animals with ALI, higher counts of cells, mainly neutrophils, in BALF and increased production of pro-inflammatory substances were observed compared with controls. SNAP therapy reduced a leak of cells into the lung and decreased concentrations of pro-inflammatory and apoptotic markers, reduced mRNA expression of iNOS, and decreased apoptotic index in the lung.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bhargava M, Wendt CH (2012) Biomarkers in acute lung injury. Transl Res 159:205–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferguson ND, Frutos-Vivar F, Esteban A, Fernandez-Segoviano P, Aramburu JA, Najera L, Stewart TE (2005) Acute respiratory distress syndrome: under recognition by clinicians and diagnostic accuracy of three clinical definitions. Crit Care Med 33:2228–2234

    Article  PubMed  Google Scholar 

  • Grommes J, Soehnlein O (2011) Contribution of neutrophils to acute lung injury. Mol Med 17:293–307

    Article  CAS  PubMed  Google Scholar 

  • Hogaboam CM, Chensue SW, Steinhauser ML, Huffnagle GB, Lukacs NW, Strieter RM, Kunkel SL (1997) Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide. J Immunol 159:5585–5593

    CAS  PubMed  Google Scholar 

  • Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE (1993) Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci U S A 90:8103–8107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelm M (1999) NO metabolism and breakdown. Biochim Biophys Acta 1411:273–289

    Article  CAS  PubMed  Google Scholar 

  • Kim YM, Talanian RV, Billiar TR (1997) Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms. J Biol Chem 272:31138–31148

    Article  CAS  PubMed  Google Scholar 

  • Kinnula VL, Adler KB, Ackley NJ, Crapo JD (1992) Release of reactive oxygen species by guinea pig tracheal epithelial cells in vitro. Am J Physiol 262:L708–L712

    CAS  PubMed  Google Scholar 

  • Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J (2001) Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 107:1529–1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamb NJ, Quinlan GJ, Westerman ST, Gutteridge JM, Evans TW (1999) Nitration of proteins in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome receiving inhaled nitric oxide. Am J Respir Crit Care Med 160:1031–1034

    Article  CAS  PubMed  Google Scholar 

  • Lang JD, McArdle PJ, O’Reilly PJ, Matalon S (2002) Oxidant-antioxidant balance in acute lung injury. Chest 122:S314–S320

    Article  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Lu MP, Du LZ, Gu WZ, Chen XX (2005) Nitric oxide inhalation inhibits inducible nitric oxide synthase but not nitrotyrosine formation and cell apoptosis in rat lungs with meconium-induced injury. Acta Pharmacol Sin 26:1123–1129

    Article  CAS  PubMed  Google Scholar 

  • Matthay MA, Zemans RL (2011) The acute respiratory distress syndrome: pathogenesis and treatment. Ann Rev Pathol 6:147–163

    Article  CAS  Google Scholar 

  • Miao CH, Sun B, Jiang H, Xue ZG, Lindwall R (2002) Pharmacodynamics and pharmacokinetics of inhaled nitric oxide in dogs with septic acute respiratory distress syndrome. Acta Pharmacol Sin 23:278–284

    CAS  PubMed  Google Scholar 

  • Mishra BB, Rathinam VA, Martens GW, Martinot AJ, Kornfeld H, Fitzgerald KA, Sassetti CM (2013) Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome- dependent processing of IL-1beta. Nat Immunol 14:52–60

    Article  CAS  PubMed  Google Scholar 

  • Mokra D, Mokry J, Drgova A, Petraskova M, Bulikova J, Calkovska A (2007) Intratracheally administered corticosteroids improve lung function in meconium-instilled rabbits. J Physiol Pharmacol 58:389–398

    PubMed  Google Scholar 

  • Nkadi PO, Merritt TA, Pillers DA (2009) An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab 97:95–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossi D, Gaidano G (2003) Messengers of cell death: apoptotic signaling in health and disease. Haematologica 88:212–218

    CAS  PubMed  Google Scholar 

  • Singleton PA, Dudek SM, Ma SF, Garcia JG (2006) Transactivation of sphingosine 1–phosphate receptors is essential for vascular barrier regulation: novel role for hyaluronan and CD44 receptor family. J Biol Chem 281:34381–34393

    Article  CAS  PubMed  Google Scholar 

  • Sun X, Singleton PA, Letsiou E et al (2012) Sphingosine-1-phosphate receptor-3 is a novel biomarker in acute lung injury. Am J Respir Cell Mol Biol 47:628–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szotowski B, Antoniak S, Goldin-Lang P, Tran QV, Pels K, Rosenthal P, Bogdanov VY, Borchert HH, Schultheiss HP, Rauch U (2007) Antioxidative treatment inhibits the release of thrombogenic tissue factor from irradiation- and cytokine-induced endothelial cells. Cardiovasc Res 73:806–812

    Article  CAS  PubMed  Google Scholar 

  • Tsao PS, Wang B, Buitrago R, Shyy JY, Cooke JP (1997) Nitric oxide regulates monocyte chemotactic protein-1. Circulation 96:934–940

    Article  CAS  PubMed  Google Scholar 

  • Uchida T, Shirasawa M, Ware LB, Kojima K, Hata Y, Makita K, Mednick G, Matthay ZA, Matthay MA (2006) Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med 173:1008–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang NC, Lu LH, Kao YH, Chau LY (2004) Heme oxygenase-1 attenuates interleukin-1β-induced nitric oxide synthase expression in vascular smooth muscle cells. J Biomed Sci 11:799–809

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank D. Kuliskova, Z. Remisova, M. Petraskova, and M. Hutko for technical assistance. In addition, we would like to thank for support by grants APVV-0435-11, APVV-15-0075, VEGA 1/0305/14, BioMed (ITMS 26220220187), and UK/28/2015.

Conflicts of Interest

The authors declare no conflict of interest in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Mokra .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kosutova, P., Mikolka, P., Kolomaznik, M., Balentova, S., Calkovska, A., Mokra, D. (2016). Effects of S-Nitroso-N-Acetyl-Penicillamine (SNAP) on Inflammation, Lung Tissue Apoptosis and iNOS Activity in a Rabbit Model of Acute Lung Injury. In: Pokorski, M. (eds) Pulmonary Infection and Inflammation. Advances in Experimental Medicine and Biology(), vol 935. Springer, Cham. https://doi.org/10.1007/5584_2016_34

Download citation

Publish with us

Policies and ethics