Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 May;65(5):1683–1687. doi: 10.1128/iai.65.5.1683-1687.1997

Porins of Pseudomonas aeruginosa induce release of tumor necrosis factor alpha and interleukin-6 by human leukocytes.

V Cusumano 1, M A Tufano 1, G Mancuso 1, M Carbone 1, F Rossano 1, M T Fera 1, F A Ciliberti 1, E Ruocco 1, R A Merendino 1, G Teti 1
PMCID: PMC175197  PMID: 9125547

Abstract

The aim of this study was to examine the ability of Pseudomonas aeruginosa components to induce release of cytokines from human leukocytes. Human whole-blood cultures were incubated with several concentrations of purified P. aeruginosa products, including porins, exomucopolysaccharide, lipopolysaccharide, and toxin A. Supernatants were assayed for tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) activities. All of the P. aeruginosa components except toxin A were able to stimulate the release of both cytokines. On a weight basis, porins were as effective as lipopolysaccharide and significantly more effective than exomucopolysaccharide in inducing IL-6 release (P < 0.05). Moreover, porins were more potent than either exomucopolysaccharide or lipopolysaccharide in inducing TNF-alpha release (P < 0.05). Further experiments using isolated leukocytes suggested that monocytes were the cell population predominantly responsible for the production of both cytokines. These data indicate that P. aeruginosa porins are able to induce significant cytokine production. These components may be responsible for the chronically overactive inflammatory response associated with persistent lung infection in cystic fibrosis patients.

Full Text

The Full Text of this article is available as a PDF (752.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aderka D., Le J. M., Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol. 1989 Dec 1;143(11):3517–3523. [PubMed] [Google Scholar]
  2. Ames G. F., Spudich E. N., Nikaido H. Protein composition of the outer membrane of Salmonella typhimurium: effect of lipopolysaccharide mutations. J Bacteriol. 1974 Feb;117(2):406–416. doi: 10.1128/jb.117.2.406-416.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borregaard N. Bactericidal mechanisms of the human neutrophil. An integrated biochemical and morphological model. Scand J Haematol. 1984 Mar;32(3):225–230. doi: 10.1111/j.1600-0609.1984.tb01685.x. [DOI] [PubMed] [Google Scholar]
  4. Bruce M. C., Poncz L., Klinger J. D., Stern R. C., Tomashefski J. F., Jr, Dearborn D. G. Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis. Am Rev Respir Dis. 1985 Sep;132(3):529–535. doi: 10.1164/arrd.1985.132.3.529. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis. 1991 Jun;163(6):1177–1184. doi: 10.1093/infdis/163.6.1177. [DOI] [PubMed] [Google Scholar]
  6. Elborn J. S., Shale D. J. Cystic fibrosis. 2. Lung injury in cystic fibrosis. Thorax. 1990 Dec;45(12):970–973. doi: 10.1136/thx.45.12.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Espevik T., Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986 Dec 4;95(1):99–105. doi: 10.1016/0022-1759(86)90322-4. [DOI] [PubMed] [Google Scholar]
  8. Evans L. R., Linker A. Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa. J Bacteriol. 1973 Nov;116(2):915–924. doi: 10.1128/jb.116.2.915-924.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galdiero F., Gorga F., Bentivoglio C., Mancuso R., Galdiero E., Tufano M. A. The action of LPS porins and peptidoglycan fragments on human spermatozoa. Infection. 1988;16(6):349–353. doi: 10.1007/BF01644545. [DOI] [PubMed] [Google Scholar]
  10. Galdiero F., Tufano M. A., Galdiero M., Masiello S., Di Rosa M. Inflammatory effects of Salmonella typhimurium porins. Infect Immun. 1990 Oct;58(10):3183–3186. doi: 10.1128/iai.58.10.3183-3186.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galdiero F., Tufano M. A., Sommese L., Folgore A., Tedesco F. Activation of complement system by porins extracted from Salmonella typhimurium. Infect Immun. 1984 Nov;46(2):559–563. doi: 10.1128/iai.46.2.559-563.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Galdiero F., de L'ero G. C., Benedetto N., Galdiero M., Tufano M. A. Release of cytokines induced by Salmonella typhimurium porins. Infect Immun. 1993 Jan;61(1):155–161. doi: 10.1128/iai.61.1.155-161.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hancock R. E., Siehnel R., Martin N. Outer membrane proteins of Pseudomonas. Mol Microbiol. 1990 Jul;4(7):1069–1075. doi: 10.1111/j.1365-2958.1990.tb00680.x. [DOI] [PubMed] [Google Scholar]
  14. Hindennach I., Henning U. The major proteins of the Excherichia coli outer cell envelope membrane. Preparative isolation of all major membrane proteins. Eur J Biochem. 1975 Nov 1;59(1):207–213. doi: 10.1111/j.1432-1033.1975.tb02443.x. [DOI] [PubMed] [Google Scholar]
  15. Hodson M. E. Immunological abnormalities in cystic fibrosis: chicken or egg? Thorax. 1980 Nov;35(11):801–806. doi: 10.1136/thx.35.11.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kunkel S. L., Standiford T., Kasahara K., Strieter R. M. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res. 1991 Jan-Feb;17(1):17–23. doi: 10.3109/01902149109063278. [DOI] [PubMed] [Google Scholar]
  17. Mancuso G., Tomasello F., Migliardo M., Delfino D., Cochran J., Cook J. A., Teti G. Beneficial effects of interleukin-6 in neonatal mouse models of group B streptococcal disease. Infect Immun. 1994 Nov;62(11):4997–5002. doi: 10.1128/iai.62.11.4997-5002.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Misfeldt M. L., Legaard P. K., Howell S. E., Fornella M. H., LeGrand R. D. Induction of interleukin-1 from murine peritoneal macrophages by Pseudomonas aeruginosa exotoxin A. Infect Immun. 1990 Apr;58(4):978–982. doi: 10.1128/iai.58.4.978-982.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morrison D. C., Betz S. J., Jacobs D. M. Isolation of a lipid A bound polypeptide responsible for "LPS-initiated" mitogenesis of C3H/HeJ spleen cells. J Exp Med. 1976 Sep 1;144(3):840–846. doi: 10.1084/jem.144.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakae T. Outer membrane of Salmonella. Isolation of protein complex that produces transmembrane channels. J Biol Chem. 1976 Apr 10;251(7):2176–2178. [PubMed] [Google Scholar]
  21. Norman D., Elborn J. S., Cordon S. M., Rayner R. J., Wiseman M. S., Hiller E. J., Shale D. J. Plasma tumour necrosis factor alpha in cystic fibrosis. Thorax. 1991 Feb;46(2):91–95. doi: 10.1136/thx.46.2.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pedersen S. S., Høiby N., Espersen F., Koch C. Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. Thorax. 1992 Jan;47(1):6–13. doi: 10.1136/thx.47.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pier G. B. Immunologic properties of Pseudomonas aeruginosa mucoid exopolysaccharide (alginate). Antibiot Chemother (1971) 1989;42:80–87. doi: 10.1159/000417608. [DOI] [PubMed] [Google Scholar]
  24. Rifkind D., Palmer J. D. Neutralization of endotoxin toxicity in chick embryos by antibiotics. J Bacteriol. 1966 Oct;92(4):815–819. doi: 10.1128/jb.92.4.815-819.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smit J., Nikaido H. Outer membrane of gram-negative bacteria. XVIII. Electron microscopic studies on porin insertion sites and growth of cell surface of Salmonella typhimurium. J Bacteriol. 1978 Aug;135(2):687–702. doi: 10.1128/jb.135.2.687-702.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Suter S., Schaad U. B., Roux L., Nydegger U. E., Waldvogel F. A. Granulocyte neutral proteases and Pseudomonas elastase as possible causes of airway damage in patients with cystic fibrosis. J Infect Dis. 1984 Apr;149(4):523–531. doi: 10.1093/infdis/149.4.523. [DOI] [PubMed] [Google Scholar]
  27. Tufano M. A., Berlingieri M. T., Sommese L., Galdiero F. Immune response in mice and effects on cells by outer membrane porins from Salmonella typhimurium. Microbiologica. 1984 Oct;7(4):353–366. [PubMed] [Google Scholar]
  28. Tufano M. A., Biancone L., Rossano F., Capasso C., Baroni A., De Martino A., Iorio E. L., Silvestro L., Camussi G. Outer-membrane porins from gram-negative bacteria stimulate platelet-activating-factor biosynthesis by cultured human endothelial cells. Eur J Biochem. 1993 Jun 15;214(3):685–693. doi: 10.1111/j.1432-1033.1993.tb17969.x. [DOI] [PubMed] [Google Scholar]
  29. Tufano M. A., Ianniello R., Galdiero M., De Martino L., Galdiero F. Effect of Salmonella typhimurium porins on biological activities of human polymorphonuclear leukocytes. Microb Pathog. 1989 Nov;7(5):337–346. doi: 10.1016/0882-4010(89)90037-5. [DOI] [PubMed] [Google Scholar]
  30. Tufano M. A., Rossano F., Catalanotti P., Liguori G., Capasso C., Ceccarelli M. T., Marinelli P. Immunobiological activities of Helicobacter pylori porins. Infect Immun. 1994 Apr;62(4):1392–1399. doi: 10.1128/iai.62.4.1392-1399.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tufano M. A., Rossano F., Catalanotti P., Liguori G., Marinelli A., Baroni A., Marinelli P. Properties of Yersinia enterocolitica porins: interference with biological functions of phagocytes, nitric oxide production and selective cytokine release. Res Microbiol. 1994 May;145(4):297–307. doi: 10.1016/0923-2508(94)90185-6. [DOI] [PubMed] [Google Scholar]
  32. Tufano M. A., Tetta C., Biancone L., Iorio E. L., Baroni A., Giovane A., Camussi G. Salmonella typhimurium porins stimulate platelet-activating factor synthesis by human polymorphonuclear neutrophils. J Immunol. 1992 Aug 1;149(3):1023–1030. [PubMed] [Google Scholar]
  33. Turner M. W., Warner J. O., Stokes C. R. Immunological studies in cystic fibrosis. Arch Dis Child. 1978 Aug;53(8):631–638. doi: 10.1136/adc.53.8.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P. G., Rubira M. R., Simpson R. J. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. doi: 10.1073/pnas.83.24.9679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  36. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES