Skip to main content
Log in

Therapeutic Effects of Hyaluronan on Smoke-induced Elastic Fiber Injury: Does Delayed Treatment Affect Efficacy?

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Aerosolized hyaluronan (HA) has been previously shown to prevent cigarette smoke-induced airspace enlargement and elastic fiber injury in mice when given concurrently with smoke. In the present study, a more stringent test of the therapeutic potential of HA was performed by delaying treatment with this agent for 1 month. After treatment with cigarette smoke for 3 h per day for 5 days per week for 1 month, mice (DBA/2J) began receiving aerosolized HA (0.1%) for 1 h prior to smoke exposure (controls were given aerosolized water). The results indicate that much of the damage to the lung elastic fibers occurred within the first several months of smoke exposure, as measured by levels of desmosine and isodesmosine (DID) in bronchoalveolar lavage fluid (BALF). In contrast to previously published studies, where concurrent administration of aerosolized HA significantly reduced BALF DID levels within 3 months of smoke exposure, the same effect was not seen until 6 months when HA treatment was delayed. However, despite the prolonged breakdown of elastic fibers in the current study, a significant reduction in airspace enlargement was observed after only 2 months of HA treatment. These findings provide further support for testing this agent in patients with pre-existing chronic obstructive pulmonary disease.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Barnes PJ, Shapiro SD, Pauwels RA (2003) Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 22:672–678

    Article  CAS  PubMed  Google Scholar 

  2. Shapiro SD (2002) Proteinases in chronic obstructive pulmonary disease. Biochem Soc Trans 30:98–102

    Article  CAS  PubMed  Google Scholar 

  3. Owen CA (2008) Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 3:253–268

    CAS  PubMed  Google Scholar 

  4. Djekic UV, Gaggar A, Weathington NM (2009) Attacking the multi-tiered proteolytic pathology of COPD: new insights from basic and translational studies. Pharmacol Ther 121:132–146

    Article  CAS  PubMed  Google Scholar 

  5. Celli BR (2000) The importance of spirometry in COPD and asthma: effect on approach to management. Chest 117(2 Suppl):15S–19S

    Article  CAS  PubMed  Google Scholar 

  6. Newell JD, Hogg JC, Snider GL (2004) Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema. Eur Respir J 23:769–775

    Article  PubMed  Google Scholar 

  7. Nakano Y, Muller NL, King GG, Niimi A, Kalloger SE, Mishima M, Pare PD (2002) Quantitative assessment of airway remodeling using high-resolution CT. Chest 122:271S–275S

    Article  PubMed  Google Scholar 

  8. Barnes PJ (2004) Mediators of chronic obstructive pulmonary disease. Pharmacol Rev 56:515–548

    Article  CAS  PubMed  Google Scholar 

  9. Tzortzaki EG, Lambiri I, Vlachaki E, Siafakas NM (2007) Biomarkers in COPD. Curr Med Chem 14:1037–1048

    Article  CAS  PubMed  Google Scholar 

  10. Ma S, Lin YY, Tartell L, Turino GM (2009) The effect of tiotropium therapy on markers of elastin degradation in COPD. Respir Res 10:12

    Article  PubMed  Google Scholar 

  11. Ma S, Lieberman S, Turino GM, Lin YY (2003) The detection and quantitation of free DID in human urine and their peptide-bound forms in sputum. Proc Natl Acad Sci USA 100:12941–12943

    Article  CAS  PubMed  Google Scholar 

  12. Boschetto P, Quintavalle S, Zeni E, Leprotti S, Potena A, Ballerin L, Papi A, Palladini G, Luisetti M, Annovazzi L, Iadorola P, De Rosa E, Fabbri LM, Mapp CE (2006) Association between markers of emphysema and more severe chronic obstructive pulmonary disease. Thorax 61:1037–1042

    Article  CAS  PubMed  Google Scholar 

  13. Fiorenza D, Viglio S, Lupi A, Baccheschi J, Tinelli C, Trisolini R, Iadarola R, Luisetti M, Snider GL (2002) Urinary desmosine excretion in acute exacerbations of COPD: a preliminary report. Respir Med 96:110–114

    Article  CAS  PubMed  Google Scholar 

  14. Viglio S, Iadorola P, Lupi A, Trisolini R, Tinelli C, Balbi B, Grassi V, Worlitzsch D, Doring G, Meloni F, Meyer KC, Dowson L, Hill SL, Stockley RA, Luisetti M (2000) MEKC of DID in urine of chronic destructive lung disease patients. Eur Respir J 15:1039–1045

    Article  CAS  PubMed  Google Scholar 

  15. Cantor JO, Cerreta JM, Ochoa M, Ma S, Chow T, Grunig G, Turino GM (2005) Aerosolized hyaluronan limits airspace enlargement in a mouse model of cigarette smoke-induced pulmonary emphysema. Exp Lung Res 31:417–430

    Article  CAS  PubMed  Google Scholar 

  16. Dunnill MS (1962) Quantitative methods in the study of pulmonary pathology. Thorax 17:320–328

    Article  Google Scholar 

  17. Mascarenhas MM, Day RM, Ochoa CD, Choi WI, Yu L, Ouyang B, Garg HG, Hales CA, Quinn DA (2004) Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression. Am J Respir Cell Mol Biol 30:51–60

    Article  CAS  PubMed  Google Scholar 

  18. McKee CM, Penno MB, Cowman M, Burdick MD, Streiter RM, Bao C, Noble PW (1996) Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. J Clin Invest 98:2403–2413

    Article  CAS  PubMed  Google Scholar 

  19. Cantor JO, Cerreta JM, Armand G, Keller S, Turino GM (1993) Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen. Exp Lung Res 19:177–192

    Article  CAS  PubMed  Google Scholar 

  20. Cantor JO, Cerreta JM, Keller S, Turino GM (1995) Modulation of airspace enlargement in elastase-induced emphysema by intratracheal instillment of hyaluronidase and hyaluronic acid. Exp Lung Res 21:423–436

    Article  CAS  PubMed  Google Scholar 

  21. Murakami H, Yoshida M, Aritomi T, Shiraishi M, Ishibashi M, Watanabe K (1998) Effects of hyaluronidase on porcine pancreatic elastase-induced lung injury. J Jpn Respir Soc 36:577–584

    CAS  Google Scholar 

  22. Cantor JO, Shteyngart B, Cerreta JM, Armand G, Liu M, Turino GM (2000) The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo. Proc Soc Exp Biol Med 225:65–71

    Article  CAS  PubMed  Google Scholar 

  23. Cantor JO, Cerreta JM, Armand G, Turino GM (1998) Aerosolized hyaluronic acid decreases alveolar injury induced by human neutrophil elastase. Proc Soc Exp Biol Med 217:471–475

    CAS  PubMed  Google Scholar 

  24. Cantor JO, Cerreta JM, Armand G, Turino GM (1997) Further investigation of the use of intratracheally administered hyaluronic acid to ameliorate elastase-induced emphysema. Exp Lung Res 23(3):229–244

    Article  CAS  PubMed  Google Scholar 

  25. Baccarani-Contri M, Vincenzi D, Cicchetti F, Mori G, Pasquali-Ronchetti I (1990) Immunocytochemical localization of proteoglycans within normal elastin fibers. Eur J Cell Biol 53:305–312

    CAS  PubMed  Google Scholar 

  26. Scott JE, Cummings C, Brass A, Chen Y (1991) Secondary and tertiary structures of hyaluronan in aqueous solution, investigated by rotary shadowing-electron microscopy and computer simulation. Hyaluronan is a very efficient network-forming polymer. Biochem J 274(Pt 3):699–705

    CAS  PubMed  Google Scholar 

  27. Nadkarni PP, Kulkarni GS, Cerreta JM, Ma S, Cantor JO (2005) Dichotomous effect of aerosolized hyaluronan in a hamster model of endotoxin-induced lung injury. Exp Lung Res 31:807–818

    Article  CAS  PubMed  Google Scholar 

  28. Cocci F, Miniati M, Monti S, Cavarra E, Gambelli F, Battolla L, Lucattelli M, Lungarella G (2002) Urinary desmosine excretion is inversely correlated with the extent of emphysema in patients with chronic obstructive pulmonary disease. Int J Biochem Cell Biol 34:594–604

    Article  CAS  PubMed  Google Scholar 

  29. Comhair SA, Erzurum SC (2002) Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol 283:L246–L255

    CAS  PubMed  Google Scholar 

  30. Baskaran S, Lakshmi S, Prasad PR (1999) Effect of cigarette smoke on lipid peroxidation and antioxidant enzymes in albino rat. Indian J Exp Biol 37:1196–2000

    CAS  PubMed  Google Scholar 

  31. Wurzel H, Yeh CC, Gairola C, Chow CK (1996) Oxidative damage and antioxidant status in the lungs and bronchoalveolar lavage fluid of rats exposed chronically to cigarette smoke. J Biochem Toxicol 10:11–17

    Google Scholar 

  32. Wright JL, Churg A (1995) Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair. Am J Physiol Lung Cell Mol Physiol 12:17–20

    Google Scholar 

Download references

Acknowledgments

This work was supported by NHLBI HL68383, the Alpha-1 Foundation, the Ned Doyle Foundation, the Charles A. Mastronardi Fund, the Franklyn Bracken Fund, and the James P. Mara Center for Lung Disease at the St. Luke’s-Roosevelt Hospital Center.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jerome O. Cantor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cantor, J.O., Cerreta, J.M., Ochoa, M. et al. Therapeutic Effects of Hyaluronan on Smoke-induced Elastic Fiber Injury: Does Delayed Treatment Affect Efficacy?. Lung 189, 51–56 (2011). https://doi.org/10.1007/s00408-010-9271-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-010-9271-2

Keywords

Navigation