Skip to main content
SpringerLink
Log in

Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid

  • Published:
Lung Aims and scope Submit manuscript

Abstract

High level ozone exposure is known to cause acute, neutrophil-independent airway hyperreactivity in the guinea pig. The precise biochemical mechanisms involved remain unclear. Because of its potential pathophysiologic importance, we examined whether a lysosomal hydrolase, N-acetyl-β-D-glucosaminidase (NAGA) was released from the airways in vivo and from bronchoalveolar cells, specifically macrophages. Muscarinic reactivity was determined by measuring specific airway resistance (sRaw) in response to increasing doses of aerosolized acetylcholine in guinea pigs that were either exposed to air or to ozone (3.0 ppm, 2 h). The ozone-exposed animals showed substantial muscarinic hyperreactivity 30 min after exposure. In addition, both total and percent released NAGA in bronchoalveolar lavage fluid obtained immediately after reactivity testing were significantly greater in the ozone-exposed group. It was also found that substantially more NAGA was released from mixed bronchoalveolar lavage cells in response to 20 µM A23187. Moreover, bronchoalveolar macrophages of ozone-exposed animals secreted more NAGA upon stimulation in vitro by either 20 µM A23187 or 200 µg/ml opsonized zymosan. We conclude that ozone-induced airway hyperreactivity in guinea pigs is associated with the presence of increased NAGA activity in bronchoalveolar fluid. Our data suggest that bronchoalveolar macrophages may, at least in part, be responsible for release of this enzyme into the airways after ozone exposure.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Agrawal KP (1981) Specific airway conductance in guinea pig: normal values and histamine-induced fall. Respir Physiol 43:23–30

    Article  PubMed  CAS  Google Scholar 

  2. Bills RF (1970) Ultrastructural alterations of alveolar tissue of mice: III Ozone. Arch Environ Health 20:468–480

    Google Scholar 

  3. Bertram TA, Overby LH, Danilowicz R, Eling TE and Brody AR (1988) Pulmonary intravascular macrophages metabolize arachidonic acid in vitro. Am Rev Respir Dis 138:936–944

    PubMed  CAS  Google Scholar 

  4. Boatman ES, Sato S, Frank R (1974) Acute effects of ozone on cat lungs. II. Structural. Am Rev Respir Dis 11:157–169

    Google Scholar 

  5. Castleman WL, Dungworth DL, Tyler WS (1973) Cytochemically detected alterations of lung acid phosphatase reactivity following ozone exposure. Lab Invest 29(3):310–319

    PubMed  CAS  Google Scholar 

  6. Caboud PG, Wroblewski F (1958) Calorimetric measurement of lactic acid dehydrogenase activity of body fluids. Am J Clin Pathol 30:234–238

    Google Scholar 

  7. Christman CA, Schwartz LW (1982) Enhanced phagocytosis by alveolar macrophages induced by short-term ozone insult. Envir Res 28:241–250

    Article  CAS  Google Scholar 

  8. Dillard CJ, Urribarri N, Reddy K, Fletcher B, Taylor S, de Lumen B, Langberg S, Tappel AL (1972) Increased lysosomal enzymes in lungs of ozoned-exposed rats. Arch Environ Health 25:426–431

    PubMed  CAS  Google Scholar 

  9. Dowell AR, Lohrbauer CL, Hurst D, Lee SD (1970) Rabbit alveolar macrophage damage caused by in vivo ozone inhalation. Arch Environ Health 21:121–127

    PubMed  CAS  Google Scholar 

  10. Drazen JM (1978) Adrenergic influences on histamine-mediated bronchoconstriction in the guinea pig. J Appl Physiol 44:340–345

    PubMed  CAS  Google Scholar 

  11. Evans MJ, Bils RF, Lossli CG (1971) Effects of ozone on cell renewal in pulmonary alveoli of aging mice. Arch Environ Health 22:450–453

    PubMed  CAS  Google Scholar 

  12. Fabbri LM, Aizawn H, Alpert SE, Walters EH, O’Bryne PM, Gold BD, Nadel JA, Holtzman MJ (1984) Airway hyperresponsiveness and changes in cell counts in bronchoalveolar lavage after ozone exposure in dogs. Am Rev Respir Dis 129:228–291

    Google Scholar 

  13. Gordon JL, MacIntyre DE, McMillan RM (1977) Effect of divalent cations on lysosomal enzyme release from macrophages. Br J Pharmacol 61:452P-453P

    PubMed  CAS  Google Scholar 

  14. Goldstein E, Barlema HC, van der Ploeg M, van Duijn P, van der Stap JGMM, Lippert W (1978) Effects of ozone on lysosomal enzymes of alveolar macrophages engaged in phagocytosis and killing of inhaled staphylococcus aureus. J Inf Dis 138(3):299–311

    CAS  Google Scholar 

  15. Holtzman MJ, Fabbri LM, O’Byrne PM, Gold BD, Aizawa H, Walters EH, Alpert SE, Nadel JA (1983) Importance of airway inflammation for hyperresponsiveness induced by ozone. Am Rev Respir Dis 127:686–690

    PubMed  CAS  Google Scholar 

  16. Hu PC, Miller FJ, Daniels MJ, Hatch GE, Graham JA, Gardner DE, Selgrade MK (1981) Protein accumulation in lung lavage fluid following ozone exposure. Envir Res 29:377–388

    Article  Google Scholar 

  17. Hurst DJ, Gardner DE, Coffin DL (1970) Effects of ozone on acid hydrolases of the pulmonary alveolar macrophage. J Reticuloendothelial Soc 8:288–300

    CAS  Google Scholar 

  18. Hurst DJ, Coffin DL (1971) Ozone effect on lysosomal hydrolases of alveolar macrophages in vitro. Arch Intern Med 127:1059–1063

    Article  PubMed  CAS  Google Scholar 

  19. Ignarro LJ (1974) Regional of lysosomal enzyme secretion: role in inflammation. Agents and Actions 4(4):241–258

    Article  PubMed  CAS  Google Scholar 

  20. Lew DB, Leslie CC, Riches DWH, Henson PM (1986) Induction of macrophage lysosomal hydrolase synthesis and secretion by β-1,3-Glucan. Cell Immun 100:340–350

    Article  Google Scholar 

  21. Martin TR, Altman LC, Albert RK, Henderson WR (1984) Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung. Am Rev Respir Dis 129:106–111

    PubMed  CAS  Google Scholar 

  22. Murlas CG, Murphy T, Lang Z (1990) HOCl causes substance P hyperresponsiveness and neutral endopeptidase hyporeactivity. Am J Physiol 258:L361–368

    PubMed  CAS  Google Scholar 

  23. Murlas CG, Roum JH (1985) Sequence of pathologic changes in the airway mucosa of guinea pigs during ozone-induced bronchial hyperreactivity. Ann Rev Resp Dis 32:316–320

    Google Scholar 

  24. Murlas CF, Roum JH (1985) Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide. J Appl Physiol 58:1630–1637

    PubMed  CAS  Google Scholar 

  25. Murlas CG, Murphy TP, Chodimella V (1990) Ozone-induced, mucosa-linked airway muscle hyperresponsiveness in the guinea pig. J Appl Physiol 69:7–13

    PubMed  CAS  Google Scholar 

  26. Roum JH, Murlas CG (1984) Ozone-induced changes in muscarinic bronchial reactivity by different testing methods. J Appl Physiol 57:1783–1789

    PubMed  CAS  Google Scholar 

  27. Roum JH, Murlas CG (1986) Effects of propranolol and indomethacin on muscarinic airway reactivity in unanesthetized guinea pigs. Proc Soc Exp Biol Med 81:569–574

    Google Scholar 

  28. Schneider C, Gennaro R, deNicola G, Romeo D (1978) Secretion of granule enzymes from alveolar macrophages. Exp Cell Res 112:249–256

    Article  PubMed  CAS  Google Scholar 

  29. Seltzer J, Bigby BG, Stulbarg M, Holtzman MJ, Nadel JA, Ueki IF, Leikauf GD, Goetzl EJ, Boushey HA (1986) Oz-induced change in bronchial reactivity to methacholine and airway inflammation in human. J Appl Physiol 60(4):1321–1326

    PubMed  CAS  Google Scholar 

  30. Stephens RJ, Sloan MF, Evans MJ, Freeman G (1974) Alveolar type I cell response to exposure to 0.5 ppm Oz for short periods. Exp Mol Pathol 20:11–23

    Article  PubMed  CAS  Google Scholar 

  31. Vanhoutte PM (1989) Epithelium-derived relaxing factor(s) and bronchial reactivity. J Allergy Clin Immunol 83:855–861

    Article  PubMed  CAS  Google Scholar 

  32. Werthamer S, Penha PD, Amaral L (1974) Pulmonary lesions induced by chronic exposure to ozone. Arch Environ Health 29:164–166

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Christopher G. Murlas

    Present address: Dept. of Medicine (Pulmonary Medicine), Rush University, 1653 West Congress Parkway, 60612, Chicago, IL, USA

Authors and Affiliations

  1. Department of Pediatrics, University of Tennessee, Memphis, Tennessee, USA

    D. Betty Lew M.D.

  2. Department of Medicine, University of Tennessee, Memphis, Tennessee, USA

    Vidyasagar Chodimella & Christopher G. Murlas

Authors
  1. D. Betty Lew M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vidyasagar Chodimella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher G. Murlas
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lew, D.B., Chodimella, V. & Murlas, C.G. Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid. Lung 168, 273–283 (1990). https://doi.org/10.1007/BF02719704

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02719704

Key words

Search

Navigation