This paper is only available as a PDF. To read, Please Download here.
Abstract
We studied the mechanism of the delay in neutrophil traffic in pulmonary microvasculature
previously observed during cigarette smoking, the effect of cigarette smoke on lung
phagocytes and epithelial cell function, and augmentation of the glutathione (GSH)
antioxidant system using the thiol drug. N-acetylcysteine. Using a micropore membrane
system to mimic the dimensions of the average pulmonary capillary, we showed that
cigarette smoke reduces cell deformability, increasing the difficulty experienced
by the larger neutrophils in negotiating the smaller capillary segments, so delaying
their passage during smoking. This effect is both diminished and recoverable by the
addition of plasma, and by GSH in concentrations found in plasma.
Cigarette smoke induces oxidative changes in both the cell membrane and the cell cytoskeleton,
and diminishes the ability of neutrophils to release reactive oxygen intermediates.
The injurious effect of oxidants can be measured in vitro by the detachment of 51Cr-radiolabeled alveolar epithelial cells grown in monolayers, an effect also diminished
by the addition of GSH. Such epithelial cell detachment in vitro may be reflected
as the epithelial permeability that occurs at an early stage in asymptomatic smokers.
N-Acetylcysteine given orally (600 mg/day) increases both plasma and bronchoalveolar
lavage GSH in normal subjects, but a sustained increase in plasma GSH requires higher
dosage regimens in patients with chronic obstructive pulmonary disease (600 mg three
times daily). Thus, the potential exists to enhance the antioxidant status of both
plasma and the airspaces of the lungs against oxidant-induced injury.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Free-radical chemistry of cigarette smoke and its toxicological implications.Environ Health Perspect. 1985; 64: 111-126
- Ozone-induced inflammation in the lower airways.Am Rev Respir Dis. 1989; 139: 407-415
- Oxidant-dependent microbial killing by phagocytes.N Engl J Med. 1978; 298: 659-668
- Oxidant injury of the extra-cellular matrix-potential role in the pathogenesis of pulmonary emphysema.Lung. 1985; 163: 1-13
- The oxidative inactivation of human alpha1-proteinase inhibitor by gas phase cigarette smoke.Biochem Biophys Res Commun. 1984; 122: 676-681
- Rapid improvement in abnormal pulmonary epithelial permeability after stopping cigarettes.Br Med J. 1981; 282: 1183-1186
- Elastases and emphysema: current assessment of the protease-antiprotease hypothesis.Am Rev Respir Dis. 1985; 132: 417-433
- Pathogenesis of emphysema.in: Assessment of basic science concepts through clinical investigations. 2nd edition. Chest. 95. 1989: 190-195
- Altered oxidative metabolic responses in vitro, of alveolar macrophages from asymptomatic cigarette smokers.Am Rev Respir Dis. 1981; 123: 85-89
- Possible mechanisms of emphysema in cigarette smokers.in: Release of elastase from human polymorphonuclear leukocytes by cigarette smoke condensate. 2nd edition. Am Rev Respir Dis. 117. 1978: 317-325
- Extracellular elastolytic activity in human lung lavage: a comparative study between smokers and non-smokers.Clin Sci. 1985; 69: 17-27
- Interactions of granulocytes with the lungs.Circ Res. 1984; 54: 623-635
- Cigarette smoking and lung destruction: accumulation of neutrophils in the lungs of cigarette smokers.Am Rev Respir Dis. 1983; 128: 833-838
- Pulmonary strategies of anti-oxidant defence.Am Rev Respir Dis. 1989; 140: 531-554
- Is antioxidant deficiency related to chronic obstructive pulmonary disease?.Am Rev Respir Dis. 1986; 134: 285-289
- Deficiency of vit E in the alveolar fluid of cigarette smokers.in: Influence on macrophage cytotoxicity. 2nd edition. J Clin Invest. 77. 1986: 789-796
- Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke exposed hamsters.Am Rev Respir Dis. 1990; 141: 678-682
- N-acetylcysteine protection against the toxicity of cigarette smoke and cigarette smoke condensates in various tissues and cells in vivo.Eur J Respir Dis. 1985; 66: 123-129
- Normal alveolar epithelial lining fluid contains high levels of glutathione.J Appl Physiol. 1987; 63: 152-157
- Neutrophil kinetics and lung injury.Physiol Rev. 1987; 67: 1249-1295
- Neutrophil kinetics in the lungs.Clin Sci. 1990; 79: 97-107
- Physiological neutrophil sequestration in the lung: visual evidence for localisation in capillaries.J Appl Physiol. 1987; 62: 1236-1243
- Regional Differences in neutrophil margination in dog lungs.J Appl Physiol. 1987; 63: 1253-1261
- Marginated pool of neutrophils in rabbit lungs.J Appl Physiol. 1987; 63: 1806-1815
- Pulmonary microcirculatory kinetics of neutrophils deficient in leukocite adhesion-promoting-glycoproteins.J Appl Physiol. 1990; 69: 207-213
- Leukocyte kinetics in the human lung: role of exercise and catecholamines.J Appl Physiol. 1984; 57: 711-719
- The effect of cigarette smoking on neutrophil kinetics in human lungs.N Engl J Med. 1989; 321: 924-928
- Regional pulmonary transit times in man.J Appl Physiol. 1989; 66: 844-850
- Neutrophil retention in the lungs of patients with chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 143: 1359-1364
- Morphometry of the human lung.Academic Press, New York1963
- Morphometry of human leukocytes.Blood. 1980; 56: 866-875
- Viscoelastic properties of leukocytes.in: Meiselman HJ Lichtman MA LeCelle PL White cell mechanics: basic science and clinical aspects. Alan R. Liss, New York1984: 19-51
- A structural model for passive granulocyte behavior based on mechanical deformation and recovery after deformation tests.in: Meiselman HJ Lichtamn MA LeCelle PA White cell mechanics: basic science and clinical aspects. Alan R. Liss, New York1984: 53-71
- Filterability of white blood cell subpopulations, separated by an improved method.Clin Haemorheol. 1987; 7: 811-816
- Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries.Science. 1989; 245: 183-185
- Neutrophil deformability in vitro determines in vivo lung retention in man.Am Rev Respir Dis. 1990; 141: A666
- Neutrophil sequestration in the lungs during smoking may result from a decrease in cell deformability.Am Rev Respir Dis. 1989; 139: A298
- A model of action of cigarette smoke on intravascular neutrophils in the lungs: mechanisms of injury and protection.Am Rev Respir Dis. 1990; 141: A640
- Neutrophil morphology following cigarette smoke exposure.Clin Sci. 1990; 78: 4
- Surface morphology and functional studies of human alveolar macrophages for cigarette smokers and non-smokers.J Reticuloendothel Soc. 1982; 32: 1-23
- Neutrophil kinetics in rat lungs.Ann NY Acad Sci. 1991; 624: 316-317
- Ozone and human blood.Arch Environ Health. 1975; 30: 40-43
Brown GM, Drost E, Lannan S, Donaldson K, MacNee W. Reduction of the proteolytic activity of neutrophils by exposure to cigarette smoke in vitro, Exp Lung Res (in press).
- The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extra-cellular matrix in vitro.Br J Exp Pathol. 1988; 69: 327-338
- Lung protection by a thiol-containing antioxidant, N-acetylcysteine.Respiration. 1986; 50: 31-42
- Acetylcysteine: a drug with an interesting past and a fascinating future.Respiration. 1986; 50: 26-30
- Oral N-acetylcysteine reduces exacerbation rate in chronic bronchitis.Eur Resp J. 1983; 64: 405-415
- Reduction in days of illness after long term treatment with N-acetylcysteine controlled release tablets in patients with chronic bronchitis.Eur Respir J. 1988; 1: 351-355
- Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitis and severe airways obstruction.Thorax. 1985; 40: 832-835
- Toxicological, pharmacokinetic and metabolic studies on acetylcysteine.Eur Respir J. 1980; 61: 45-51
- Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.Thorax. 1991; 46: 39-42
- Effect of N-acetylcysteine on low molecular weight thiols in plasma.Am Rev Respir Dis. 1990; 141: A650
- The effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages.Thorax. 1989; 44: 359
Article info
Footnotes
☆This work was supported by Zambon Research and the Norman Salvesen Emphysema Research Fund.
Identification
Copyright
© 1991 Published by Elsevier Inc.
