Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1988;166(1):355–369. doi: 10.1007/BF02714068

A reversible model of acute lung injury based on ozone exposure

D J P Bassett 1,✉, E Bowen-Kelly 1, E L Brewster 1, C L Elbon 1, S S Reichenbaugh 1, T Bunton 3, J S Kerr 4
PMCID: PMC7087886  PMID: 3148794

Abstract

In this study inflammatory responses were determined in rat lungs 0, 1, 3, and 8 days following single 2- and 4-hr exposures to 1.8 ppm ozone. Analysis of lavage fluid immediately following exposure demonstrated enhanced lactate dehydrogenase activity and decreased numbers of lavageable macrophages but no alterations in albumin content. Similar analyses at one day postexposure demonstrated 282% and 456% increases in albumin content and enhanced numbers of lavageable neutrophils from a control value of 0.01 ± 0.01 to 0.27 ± 0.10 and 0.78 ± 0.11 million cells per lung for 2-hr and 4-hr exposures, respectively. The observed increased levels of albumin were also present at 3 days, at which time the number of lavageable neutrophils was not significantly different than control. At both one and 3 days postexposure, lavageable lymphocytes were significantly increased 10-fold from a control value of 0.03 ± 0.01 million cells per lung. However, the number of lavageable macrophages was unaltered on day 1, but enhanced on day 3, giving values of 0.67 ± 0.05 (control), 2.25 ± 0.46 (2 hr), and 2.70 ± 1.05 (4 hr) million cells per lung. By 8 days both inflammatory cell numbers and albumin levels had returned to control values. Since these data demonstrated different time courses for each inflammatory cell type, this reversible model of acute lung injury should be useful for establishing possible involvement of these cells in processes of lung injury.

Key words: Inflammatory cells, Macrophages, Neutrophils, Vascular permeability

References

  • 1.Alpert SM, Schwartz BB, Lee SD, Lewis TR. Alveolar protein accumulation—A sensitive indicator of low oxidant toxicity. Arch Intern Med. 1971;128:69–73. doi: 10.1001/archinte.128.1.69. [DOI] [PubMed] [Google Scholar]
  • 2.Autor AP, Schmitt SL. Pulmonary fibrosis and paraquat toxicity. In: Autor, editor. Biochemical mechanisms of paraquat toxicity. New York: Academic Press; 1977. pp. 175–186. [Google Scholar]
  • 3.Bassett DJP, Fisher AB. Metabolic responses to carbon monoxide by isolated rat lungs. Am J Physiol. 1976;230:658–663. doi: 10.1152/ajplegacy.1976.230.3.658. [DOI] [PubMed] [Google Scholar]
  • 4.Bergmeyer HU. Methods of enzymatic analysis, vol 3. Deerfield Beech: Verlag-Chemie; 1983. Lactate dehydrogenase; pp. 118–126. [Google Scholar]
  • 5.Burton K. A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956;62:315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Coffin DL, Gardner DE, Holzman RS, Wolock FJ. Influence of ozone on pulmonary cells. Arch Environ Health. 1968;16:633–636. doi: 10.1080/00039896.1968.10665119. [DOI] [PubMed] [Google Scholar]
  • 7.Dowdy S, Wearden S. Statistics for research, chap 11. New York: Wiley; 1983. pp. 173–200. [Google Scholar]
  • 8.Evans MJ, Johnson LV, Stephens RJ, Freeman G. Cell renewal in the lungs of rats exposed to low levels of ozone. Exp Molec Pathol. 1976;24:70–83. doi: 10.1016/0014-4800(76)90058-7. [DOI] [PubMed] [Google Scholar]
  • 9.Fisher HK, Clements JA, Wright RR. Pulmonary effects of the herbicide paraquat studied 3 days after injection in rats. J Appl Physiol. 1973;35:268–273. doi: 10.1152/jappl.1973.35.2.268. [DOI] [PubMed] [Google Scholar]
  • 10.Guth DJ, Warren DL, Last JA. Comparative sensitivity of measurements of lung damage made by bronchoalveolar lavage after short-term exposure of rats to ozone. Toxicology. 1986;40:131–143. doi: 10.1016/0300-483X(86)90074-0. [DOI] [PubMed] [Google Scholar]
  • 11.Hesterberg TW, Gerriets JE, Reiser KM, Jackson AC, Cross CE, Last JA. Bleomycin-induced pulmonary fibrosis: Correlation of biochemical, physiological, and histological changes. Toxicol Appl Pharmacol. 1981;60:360–367. doi: 10.1016/0041-008X(91)90239-B. [DOI] [PubMed] [Google Scholar]
  • 12.Hesterberg TW, Last JA. Ozone-induced acute pulmonary fibrosis in rats—Prevention of increased rates of collagen synthesis by methylprednisolone. Am Rev Respir Dis. 1981;123:47–52. doi: 10.1164/arrd.1981.123.1.47. [DOI] [PubMed] [Google Scholar]
  • 13.Hocking WG, Golde DW. The pulmonary-alveolar macrophage. New Eng J Med. 1979;301:639–645. doi: 10.1056/NEJM197909203011205. [DOI] [PubMed] [Google Scholar]
  • 14.Huber GL, Mason RJ, LaForce M, Spencer NJ, Gardner DE, Coffin DL. Alterations in the lung following the administration of ozone. Arch Intern Med. 1971;128:81–87. doi: 10.1001/archinte.128.1.81. [DOI] [PubMed] [Google Scholar]
  • 15.Johnson KJ, Fantone JC, Kaplan J, Ward PA. In vivo damage of rat lungs by oxygen metabolites. J Clin Invest. 1981;67:983–993. doi: 10.1172/JCI110149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Johnson KJ, Ward PA. Acute and progressive lung injury after contact with phorbol myristate acetate. Am J Pathol. 1982;107:29–35. [PMC free article] [PubMed] [Google Scholar]
  • 17.Katzenstein A-LA, Bloor CM, Leibow AA. Diffuse alveolar damage—The role of oxygen, shock, and related factors. Am J Pathol. 1981;85:210–228. [PMC free article] [PubMed] [Google Scholar]
  • 18.Kerr JS, Ciuffetelli A, Hall HD, Stevens TM, Ackerman NR, Mackin WM. Acute lung inflammation in rats induced by phorbol myristate acetate (PMA) Agents Actions. 1987;21:293–296. doi: 10.1007/BF01966495. [DOI] [PubMed] [Google Scholar]
  • 19.Menzel DB. Oxidation of biologically active reducing substances by ozone. Arch Environ Health. 1971;23:149–153. doi: 10.1080/00039896.1971.10665973. [DOI] [PubMed] [Google Scholar]
  • 20.Menzel DB. The role of free radicals in the toxicity of air pollutants (nitrogen oxides and ozone) In: Pryor WA, editor. Free radicals in biology, vol. 2. New York: Academic Press; 1976. pp. 181–202. [Google Scholar]
  • 21.Munro HN, Fleck A. The determination of nucleic acids. Methods Biochem Anal. 1966;14:113–176. doi: 10.1002/9780470110324.ch5. [DOI] [PubMed] [Google Scholar]
  • 22.Mustafa MG, Tierney DF. Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Respir Dis. 1978;118:1061–1091. doi: 10.1164/arrd.1978.118.6.1061. [DOI] [PubMed] [Google Scholar]
  • 23.Nathan CF, Murray HW, Cohn ZA. The macrophage as an effector cell. New Engl J Med. 1980;303:622–626. doi: 10.1056/NEJM198009113031106. [DOI] [PubMed] [Google Scholar]
  • 24.Rabinowitz JL, Bassett DJP. Effect of 2 ppm ozone exposure on rat lung lipid fatty acids. Exper Lung Res. 1988;14:477–489. doi: 10.3109/01902148809087822. [DOI] [PubMed] [Google Scholar]
  • 25.Repine JE. Neutrophils, oxygen radicals, and the adult respiratory distress syndrome. In: Said SA, editor. The pulmonary circulation and acute lung injury, chap 11. Mount Kisco: Futura; 1985. pp. 249–281. [Google Scholar]
  • 26.Rodkey FL. Direct spectrophotometric determination of albumin in human serum. Clin Chem. 1965;11:478–487. [PubMed] [Google Scholar]
  • 27.Roth RA. Effect of pneumotoxicants on lactate dehydrogenase activity in airways of rats. Toxicol Appl Pharmacol. 1981;57:69–78. doi: 10.1016/0041-008X(81)90026-0. [DOI] [PubMed] [Google Scholar]
  • 28.Schraufstatter IU, Revak SD, Cochrane CG. Proteases and oxidants in experimental pulmonary inflammatory injury. J Clin Invest. 1984;73:1175–1184. doi: 10.1172/JCI111303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Shasby DM, Vanbenthuysen KM, Tate RM, Shasby SS, McMurtry I, Repine JE. Granulocytes mediate acute edematous lung injury in rabbits and isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals. Am Rev Respir Dis. 1982;125:443–447. doi: 10.1164/arrd.1982.125.4.443. [DOI] [PubMed] [Google Scholar]
  • 30.Stegemann H, Stalder K. Determination of hydroxyproline. Clin Chem Acta. 1967;18:207–273. doi: 10.1016/0009-8981(67)90167-2. [DOI] [PubMed] [Google Scholar]
  • 31.Stokinger HE. Ozone toxicology. Arch Environ Health. 1965;10:719–731. doi: 10.1080/00039896.1965.10664082. [DOI] [PubMed] [Google Scholar]
  • 32.Thrall RS, Barton RW. A comparison of lymphocyte populations in lung tissue and in bronchoalveolar lavage fluid of rats at various times during the development of bleomycin-induced pulmonary fibrosis. Am Rev Respir Dis. 1984;129:279–283. [PubMed] [Google Scholar]
  • 33.Warr GA, Jakab GJ. Pulmonary inflammatory responses during viral pneumonia and secondary bacterial infection. Inflammation. 1983;7:93–104. doi: 10.1007/BF00917815. [DOI] [PubMed] [Google Scholar]

Articles from Lung are provided here courtesy of Nature Publishing Group

RESOURCES