Skip to main content
Log in

Nicotine-induced release of elastase and eicosanoids by human neutrophils

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

We examined the direct effects of nicotine on a variety of neutrophil functions at concentrations achievable in lung and oral tissues from cigarette smoking. The results show dose-dependent suppression of chemotaxis and phagocytosis, and enhancement of degranulation and eicosanoid generation, but not superoxide production. Cell viability was not affected by the concentrations of nicotine used in these experiments, as shown by trypan blue dye exclusion and MTT assays. These results implicate nicotine as the ingredient in cigarette smoke responsible for inflammatory damage to lungs and oral tissues observed in cigarette smokers.

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

Similar content being viewed by others

References

  1. Benowitz, N. L. 1988. Clinical pharmacology of nicotine.Annu. Rev. Med. 37:21–32.

    Google Scholar 

  2. Korman, M. G., R. G. Shaw, J. Hansky, G. T. Schmidt, andA. I. Stern. 1981. Influence of smoking on healing rate of duodenal ulcer in response to cimetidine on high-dose antacid.Gastroenterology 80:1451–1453.

    PubMed  Google Scholar 

  3. Murthy, S. N. S., V. P. Dinoso, H. R. Clearfield, andW. V. Chey. 1977. Simultaneous measurement of basal pancreatic, gastric acid secretion, plasma gastrin and secretion during smoking.Gastroenterology 73:758–761.

    PubMed  Google Scholar 

  4. Brischetto, C. S., W. E. Connor, S. I. Connor, andJ. D. Matarazzo. 1983. Plasma lipid and lipoprotein profiles of cigarette smoking from randomly selected families: Enhancement of hyperlipidemia and depression of high-density lipoprotein.Am. J. Cardiol. 52:675–680.

    PubMed  Google Scholar 

  5. Billimoria, J. D., H. Pozner, H. B. Metselaar, F. W. Best, andD. O. James. 1975. Effect of cigarette smoking on lipids, lipoproteins, blood coagulation, fibrinolysis and cellular components of human blood.Atherosclerosis 21:61–76.

    PubMed  Google Scholar 

  6. Renaud, S., D. Blache, E. Dumont, C. Thevenon, andC. Wissendanger. 1984. Platelet function after cigarette smoking in relation to nicotine and carbon monoxide.Clin. Pharmacol. Ther. 36:389–395.

    PubMed  Google Scholar 

  7. Hoffman, D., andK. D. Brunnemann. 1983. Endogenous formation ofN-nitrosoproline in cigarette smokers.Cancer Res. 43:5570–5576.

    PubMed  Google Scholar 

  8. Totti, N., K. T. McCusker, E. J. Campbell, G. I. Griffin, andR. M. Senior. 1984. Nicotine is chemotactic for neutrophils and enhances neutrophil responsiveness to chemotactic peptides.Science 223:169–171.

    PubMed  Google Scholar 

  9. Nowak, D., U. Ruta, andG. Piasecka. 1990. Nicotine increases human polymorphonuclear leukocytes chemotactic response—a possible additional mechanism of lung injury in cigarette smokers.Exp. Pathol. 39:37–43.

    PubMed  Google Scholar 

  10. Corberand, J. P. LaHarrague, F. Nguyen, G. Dutau, M. Fontanilles, B. Gleizes, andE. Gyrard. 1980. In vitro effect of tobacco smoke components on the functions of normal human polymorphonuclear leukocytes.Infect. Immun. 30:649–655.

    PubMed  Google Scholar 

  11. Bridges, R. B., J. H. Kraal, J. T. Huang, andM. B. Chancellor. 1977. Effects of tobacco smoke on chemotaxis and glucose metabolism of polymorphonuclear leukocytes.Infect. Immun. 15:115–123.

    PubMed  Google Scholar 

  12. Ferrante, A., andY. H. Thong. 1980. Optimal conditions for simultaneous purification of mononuclear and polymorphonuclear leukocytes from human blood by the hypaque-ficoll method.J. Immunol. Methods 36:109–117.

    PubMed  Google Scholar 

  13. Nelson, R. D., P. G. Quie, andR. L. Simmons. 1975. Chemotaxis under agarose: A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes.J. Immunol. 115:1650–1656.

    PubMed  Google Scholar 

  14. Seow, W. K., A. Ferrante, S. Y. Li, andY. H. Thong. 1988. Antiphagocytic and antioxidant properties of plant alkaloid tetrandrine.Int. Arch. Allergy Appl. Immunol. 85:404–407.

    PubMed  Google Scholar 

  15. MacFarlane, G. D., andM. C. Herzberg. 1984. Concurrent estimation of the kinetics of adhesion and ingestion ofStaphylococcus aureus by human polymorphonuclear leukocytes (PMNs).J. Immunol. Methods. 66:35–49.

    PubMed  Google Scholar 

  16. West, B. C., A. S. Rosenthal, N. A. Gelb, andH. R. Kimball. 1974. Separation and characterization of human neutrophil granules.Am. J. Pathol. 77:41–49.

    PubMed  Google Scholar 

  17. Gallin, J. I., M. P. Fletcher, B. E. Seligmann, S. Hoffstein, K. Cehrs, andN. Mounessa. 1982. Human neutrophil-specific granule deficiency: A model to assess the role of neutrophilspecific granules in the evolution of the inflammatory response.Blood. 54:1317–1329.

    Google Scholar 

  18. Babior, B. M., R. S. Kipnes, andJ. Curnette. 1970. Biological defence mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent.J. Clin. Invest. 52:791–744.

    Google Scholar 

  19. Teh, B. S., W. K. Seow, S. Y. Li, andY. H. Thong. 1990. Inhibition of prostaglandin and leukotriene production by the plant alkaloids tetrandrine and berbamine.Int. J. Immunopharmacol. 12:321–326.

    PubMed  Google Scholar 

  20. Pruett, S. B., andA. Y. Loftis. 1990. Characteristics of MTT as an indicator of viability and respiratory burst activity of human neutrophils.Int. Arch. Allergy Appl. Immunol. 92:189–192.

    PubMed  Google Scholar 

  21. Janoff, A. 1983. Biochemical links between cigarette smoking and pulmonary emphysema.J. Appl. Physiol. 55:285–293.

    PubMed  Google Scholar 

  22. Gadek, J. E., G. A. Fells, andR. G. Crystal. 1979. Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans.Science 206:1315–1316.

    PubMed  Google Scholar 

  23. Stone, P. J., J. D. Calore, S. E. McGowan, J. Bernardo, G. L. Snider, andC. Franzblau. 1983. Functionalα 1-protease inhibitor in the lower respiratory tract of cigarette smokers is not decreased.Science 221:1187–1189.

    PubMed  Google Scholar 

  24. Hunninghake, G. W., andR. G. Crystal. 1983. Cigarette smoking and lung destruction.Am. Rev. Respir. Dis. 128:833–838.

    PubMed  Google Scholar 

  25. Weiss, S. J. 1989. Tissue destruction by neutrophils.N. Eng. J. Med. 320:365–376.

    Google Scholar 

  26. MacNee, W., B. Wiggs, S. A. Belzberg, andJ. C. Hogg. 1989. The effect of cigarette smoking on neutrophil kinetics in human lungs.N. Engl. J. Med. 321:924–925.

    PubMed  Google Scholar 

  27. Abboud, R. T., T. Fera, S. Johal, A. Richter, andN. Gibson. 1986. Effect of smoking on plasma neutrophil elastase levels.J. Lab. Clin. Med. 108:294–300.

    PubMed  Google Scholar 

  28. Weitz, J. I., K. A. Crowley, S. L. Landman, B. Lipman, andJ. Yu. 1987. Increased neutrophil elastase activity in cigarette smokers.Ann. Int. Med. 107:680–682.

    PubMed  Google Scholar 

  29. Janoff, A. 1985. Elastase in tissue injury.Annu. Rev. Med. 36:207–216.

    PubMed  Google Scholar 

  30. Rosenberg, J., N. L. Benowitz, P. Jacob, andK. M. Wilson. 1980. Disposition kinetics and effects of intravenous nicotine.Clin. Pharmacol. 28:517–522.

    Google Scholar 

  31. Benowitz, N. L., P. Jacob, R. T. Jones, andJ. Rosenberg. 1982. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man.J. Pharmacol. Exp. Ther. 221:368–372.

    PubMed  Google Scholar 

  32. Feyerabend, C., T. Higenbottam, andM. A. Russell. 1982. Nicotine concentrations in urine and saliva of smokers and non-smokers.Br. Med. J. 284:1002–1004.

    Google Scholar 

  33. Jacob, P., M. Wilson, andN. L. Benowitz. 1981. Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids.J. Chromotogr. 222:61–70.

    Google Scholar 

  34. Russell, M. A. H., C. Feyerand, andP. V. Cole. 1976. Plasma nicotine levels after cigarettes smoking and chewing nicotine gum.Br. Med. J. 1:1043–1046.

    PubMed  Google Scholar 

  35. Benowitz, N. L. 1983. Smokers of low-yield cigarettes do not consume less nicotine.N. Engl. J. Med. 309:139–142.

    PubMed  Google Scholar 

  36. Benowitz, N. L., andP. Jacob, III. 1984. Daily intake of nicotine during cigarette smoking.Clin. Pharmocol. Ther. 35:499–504.

    Google Scholar 

  37. Bergstrom, J., andS. Eliasson. 1987. Cigarette smoking and alveolar bone height in subjects with a high standard of oral hygiene.J. Clin. Periodontol. 14:466–499.

    PubMed  Google Scholar 

  38. Goultschin, J., H. D. Sgan, M. Cohen, L. Brayer Donchin, andW. A. Soskolne. 1990. Association of smoking with periodontal treatment needs.J. Periodontal. 64:364–367.

    Google Scholar 

  39. Stoltenberg, J. L., J. B. Osborn, N. A. Hardie, M. C. Herzberg, andB. L. Philstrom. 1991. The association between periodontal status in cigarette smoking.J. Dent. Res. 70:556.

    Google Scholar 

  40. Dunford, R. G., E. Lyon, A. W. Ho, E. E. Machtei, L. A. Christersson, S. G. Grossi, andR. J. Genco. 1991. Smoking as a significant risk indicator for severe adult periodontal disease.J. Dent. Res. 70:590.

    Google Scholar 

  41. MacFarlane, G. D., M. C. Herzberg, L. F. Wolff, andN. A. Hardie. 1992. Refractory periodontitis associated with abnormal polymorphonuclear leukocyte phagocytosis and cigarette smoking.J. Periodontal. 63:908–913.

    Google Scholar 

  42. Hoffman, D., andJ. D. Adams. 1981. Carcinogenic tobacco-specificn-nitrosamines in snuff and in the saliva of snuff dippers.Cancer Res. 41:4305–4308.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seow, W.K., Thong, Y.H., Nelson, R.D. et al. Nicotine-induced release of elastase and eicosanoids by human neutrophils. Inflammation 18, 119–127 (1994). https://doi.org/10.1007/BF01534553

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01534553

Keywords

Navigation