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.
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Alpert SM, Schwartz BB, Lee SD, Lewis TR (1971) Alveolar protein accumulation—A sensitive indicator of low oxidant toxicity. Arch Intern Med 128:69–73
Autor AP, Schmitt SL (1977) Pulmonary fibrosis and paraquat toxicity. In: Autor (ed) Biochemical mechanisms of paraquat toxicity. Academic Press, New York, pp. 175–186
Bassett DJP, Fisher AB (1976) Metabolic responses to carbon monoxide by isolated rat lungs. Am J Physiol 230:658–663
Bergmeyer HU (1983). Lactate dehydrogenase. In: Methods of enzymatic analysis, vol 3. Verlag-Chemie, Deerfield Beech, pp. 118–126
Burton K (1956) A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323
Coffin DL, Gardner DE, Holzman RS, Wolock FJ (1968) Influence of ozone on pulmonary cells. Arch Environ Health 16:633–636
Dowdy S, Wearden S (1983) In: Statistics for research, chap 11. Wiley New York, pp. 173–200
Evans MJ, Johnson LV, Stephens RJ, Freeman G (1976) Cell renewal in the lungs of rats exposed to low levels of ozone. Exp Molec Pathol 24:70–83
Fisher HK, Clements JA, Wright RR (1973) Pulmonary effects of the herbicide paraquat studied 3 days after injection in rats. J Appl Physiol 35:268–273
Guth DJ, Warren DL, Last JA (1986) Comparative sensitivity of measurements of lung damage made by bronchoalveolar lavage after short-term exposure of rats to ozone. Toxicology 40:131–143
Hesterberg TW, Gerriets JE, Reiser KM, Jackson AC, Cross CE, Last JA (1981) Bleomycin-induced pulmonary fibrosis: Correlation of biochemical, physiological, and histological changes. Toxicol Appl Pharmacol 60:360–367
Hesterberg TW, Last JA (1981) Ozone-induced acute pulmonary fibrosis in rats—Prevention of increased rates of collagen synthesis by methylprednisolone. Am Rev Respir Dis 123:47–52
Hocking WG, Golde DW (1979) The pulmonary-alveolar macrophage. New Eng J Med 301:639–645
Huber GL, Mason RJ, LaForce M, Spencer NJ, Gardner DE, Coffin DL (1971) Alterations in the lung following the administration of ozone. Arch Intern Med 128:81–87
Johnson KJ, Fantone JC, Kaplan J, Ward PA (1981) In vivo damage of rat lungs by oxygen metabolites. J Clin Invest 67:983–993
Johnson KJ, Ward PA (1982) Acute and progressive lung injury after contact with phorbol myristate acetate. Am J Pathol 107:29–35
Katzenstein A-LA, Bloor CM, Leibow AA (1981) Diffuse alveolar damage—The role of oxygen, shock, and related factors. Am J Pathol 85:210–228
Kerr JS, Ciuffetelli A Jr., Hall HD, Stevens TM, Ackerman NR, Mackin, WM (1987) Acute lung inflammation in rats induced by phorbol myristate acetate (PMA). Agents Actions 21:293–296
Menzel DB (1971) Oxidation of biologically active reducing substances by ozone. Arch Environ Health 23:149–153
Menzel DB (1976) The role of free radicals in the toxicity of air pollutants (nitrogen oxides and ozone). In: Pryor WA (ed) Free radicals in biology, vol. 2. Academic Press, New York, pp. 181–202
Munro HN, Fleck A (1966) The determination of nucleic acids. Methods Biochem Anal 14:113–176
Mustafa MG, Tierney DF (1978) Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Respir Dis 118:1061–1091
Nathan CF, Murray HW, Cohn ZA (1980) The macrophage as an effector cell New Engl J Med 303:622–626
Rabinowitz JL, Bassett DJP (1988) Effect of 2 ppm ozone exposure on rat lung lipid fatty acids. Exper Lung Res 14:477–489
Repine JE (1985) Neutrophils, oxygen radicals, and the adult respiratory distress syndrome. In: Said SA (ed) The pulmonary circulation and acute lung injury, chap 11. Futura, Mount Kisco, pp. 249–281
Rodkey FL (1965) Direct spectrophotometric determination of albumin in human serum. Clin Chem 11:478–487
Roth RA (1981) Effect of pneumotoxicants on lactate dehydrogenase activity in airways of rats. Toxicol Appl Pharmacol 57:69–78
Schraufstatter IU, Revak SD, Cochrane CG (1984) Proteases and oxidants in experimental pulmonary inflammatory injury. J Clin Invest 73:1175–1184
Shasby DM, Vanbenthuysen KM, Tate RM, Shasby SS, McMurtry I, Repine JE (1982) 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 125:443–447
Stegemann H, Stalder K (1967) Determination of hydroxyproline. Clin Chem Acta 18:207–273
Stokinger HE (1965) Ozone toxicology. Arch Environ Health 10:719–731
Thrall RS, Barton RW (1984) 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 129:279–283
Warr GA, Jakab GJ (1983) Pulmonary inflammatory responses during viral pneumonia and secondary bacterial infection. Inflammation 7:93–104
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Bassett, D.J.P., Bowen-Kelly, E., Brewster, E.L. et al. A reversible model of acute lung injury based on ozone exposure. Lung 166, 355–369 (1988). https://doi.org/10.1007/BF02714068
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DOI: https://doi.org/10.1007/BF02714068