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. 1992 Feb;75(2):275–280.

Protein kinase C activation modulates tumour necrosis factor-alpha priming of human neutrophils for zymosan-induced leukotriene B4 release.

M M Petersen 1, R Steadman 1, J D Williams 1
PMCID: PMC1384706  PMID: 1312994

Abstract

Neutrophil (PMN) activation by the yeast component zymosan involves the complement receptor type 3 (CD11b/CD18). Recombinant human tumour necrosis factor-alpha (rhTNF-alpha) augmented the zymosan-stimulated leukotriene B4 (LTB4) release from PMN, reaching a fourfold increase at 10(-9) M. Co-incubation of PMN with 10(-9) M rhTNF-alpha and staurosporine resulted in a further dose-dependent increase, which became significantly greater than a purely additive effect at a staurosporine concentration of 10 nM. This synergy was maintained at all doses of staurosporine tested. In addition, doses of phorbol 12-myristate 13-acetate (PMA) that do not activate protein kinase C (PKC) (below 10(-9) M) also augmented the zymosan-stimulated release of LTB4. However, doses of PMA above 10(-9) M progressively inhibited the response to levels below that of zymosan alone. Staurosporine at 50 nM completely prevented, and 10(-9) M rhTNF-alpha partially but significantly (P less than 0.02 at 10(-8) M PMA, P less than 0.01 at 10(-7) M PMA) reversed, this high-dose PMA inhibition. PKC activation thus opposes the priming effect of rhTNF-alpha on neutrophils, while PKC inhibition may enhance the ability of rhTNF-alpha to prime PMN for zymosan activation. The combined effect of rhTNF-alpha and staurosporine suggests an intracellular synergy rather than simply a direct action due to increased zymosan receptor expression. Thus there appear to be mechanisms whereby the responses of neutrophils may be augmented without activating PKC. Indeed, kinase activation may even exert a degree of feedback control that is antagonized by rhTNF-alpha treatment.

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Selected References

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  1. Atkinson Y. H., Murray A. W., Krilis S., Vadas M. A., Lopez A. F. Human tumour necrosis factor-alpha (TNF-alpha) directly stimulates arachidonic acid release in human neutrophils. Immunology. 1990 May;70(1):82–87. [PMC free article] [PubMed] [Google Scholar]
  2. Berkow R. L., Dodson M. R. Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor. J Leukoc Biol. 1988 Nov;44(5):345–352. doi: 10.1002/jlb.44.5.345. [DOI] [PubMed] [Google Scholar]
  3. Berkow R. L., Wang D., Larrick J. W., Dodson R. W., Howard T. H. Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor. J Immunol. 1987 Dec 1;139(11):3783–3791. [PubMed] [Google Scholar]
  4. Corbi A. L., Kishimoto T. K., Miller L. J., Springer T. A. The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. J Biol Chem. 1988 Sep 5;263(25):12403–12411. [PubMed] [Google Scholar]
  5. Ferrante A., Nandoskar M., Walz A., Goh D. H., Kowanko I. C. Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. Int Arch Allergy Appl Immunol. 1988;86(1):82–91. doi: 10.1159/000234610. [DOI] [PubMed] [Google Scholar]
  6. Ferrante A. Tumor necrosis factor alpha potentiates neutrophil antimicrobial activity: increased fungicidal activity against Torulopsis glabrata and Candida albicans and associated increases in oxygen radical production and lysosomal enzyme release. Infect Immun. 1989 Jul;57(7):2115–2122. doi: 10.1128/iai.57.7.2115-2122.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Helfman D. M., Appelbaum B. D., Vogler W. R., Kuo J. F. Phospholipid-sensitive Ca2+-dependent protein kinase and its substrates in human neutrophils. Biochem Biophys Res Commun. 1983 Mar 29;111(3):847–853. doi: 10.1016/0006-291x(83)91376-1. [DOI] [PubMed] [Google Scholar]
  8. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem. 1985 Sep 2;151(2):431–437. doi: 10.1111/j.1432-1033.1985.tb09120.x. [DOI] [PubMed] [Google Scholar]
  9. Kikuchi A., Ikeda K., Kozawa O., Takai Y. Modes of inhibitory action of protein kinase C in the chemotactic peptide-induced formation of inositol phosphates in differentiated human leukemic (HL-60) cells. J Biol Chem. 1987 May 15;262(14):6766–6770. [PubMed] [Google Scholar]
  10. Kishimoto T. K., O'Connor K., Lee A., Roberts T. M., Springer T. A. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. doi: 10.1016/0092-8674(87)90246-7. [DOI] [PubMed] [Google Scholar]
  11. Klebanoff S. J., Vadas M. A., Harlan J. M., Sparks L. H., Gamble J. R., Agosti J. M., Waltersdorph A. M. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed] [Google Scholar]
  12. Kumaratilake L. M., Ferrante A., Rzepczyk C. The role of T lymphocytes in immunity to Plasmodium falciparum. Enhancement of neutrophil-mediated parasite killing by lymphotoxin and IFN-gamma: comparisons with tumor necrosis factor effects. J Immunol. 1991 Jan 15;146(2):762–767. [PubMed] [Google Scholar]
  13. Laudanna C., Miron S., Berton G., Rossi F. Tumor necrosis factor-alpha/cachectin activates the O2(-)-generating system of human neutrophils independently of the hydrolysis of phosphoinositides and the release of arachidonic acid. Biochem Biophys Res Commun. 1990 Jan 15;166(1):308–315. doi: 10.1016/0006-291x(90)91946-p. [DOI] [PubMed] [Google Scholar]
  14. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  15. Meyer T., Regenass U., Fabbro D., Alteri E., Rösel J., Müller M., Caravatti G., Matter A. A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity. Int J Cancer. 1989 May 15;43(5):851–856. doi: 10.1002/ijc.2910430519. [DOI] [PubMed] [Google Scholar]
  16. Miller L. J., Bainton D. F., Borregaard N., Springer T. A. Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest. 1987 Aug;80(2):535–544. doi: 10.1172/JCI113102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nathan C., Sanchez E. Tumor necrosis factor and CD11/CD18 (beta 2) integrins act synergistically to lower cAMP in human neutrophils. J Cell Biol. 1990 Nov;111(5 Pt 1):2171–2181. doi: 10.1083/jcb.111.5.2171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  19. O'Flaherty J. T., Jacobson D. P., Redman J. F. Bidirectional effects of protein kinase C activators. Studies with human neutrophils and platelet-activating factor. J Biol Chem. 1989 Apr 25;264(12):6836–6843. [PubMed] [Google Scholar]
  20. O'Shea J. J., Brown E. J., Seligmann B. E., Metcalf J. A., Frank M. M., Gallin J. I. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol. 1985 Apr;134(4):2580–2587. [PubMed] [Google Scholar]
  21. Petersen M., Steadman R., Hallett M. B., Matthews N., Williams J. D. Zymosan-induced leukotriene B4 generation by human neutrophils is augmented by rhTNF-alpha but not chemotactic peptide. Immunology. 1990 May;70(1):75–81. [PMC free article] [PubMed] [Google Scholar]
  22. Porteu F., Nathan C. Shedding of tumor necrosis factor receptors by activated human neutrophils. J Exp Med. 1990 Aug 1;172(2):599–607. doi: 10.1084/jem.172.2.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Richter J., Andersson T., Olsson I. Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrophil degranulation. J Immunol. 1989 May 1;142(9):3199–3205. [PubMed] [Google Scholar]
  24. Ross G. D., Cain J. A., Lachmann P. J. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed] [Google Scholar]
  25. Roubin R., Elsas P. P., Fiers W., Dessein A. J. Recombinant human tumour necrosis factor (rTNF)2 enhances leukotriene biosynthesis in neutrophils and eosinophils stimulated with the Ca2+ ionophore A23187. Clin Exp Immunol. 1987 Nov;70(2):484–490. [PMC free article] [PubMed] [Google Scholar]
  26. Schleiffenbaum B., Fehr J. The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. J Clin Invest. 1990 Jul;86(1):184–195. doi: 10.1172/JCI114683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
  28. Smith C. D., Uhing R. J., Snyderman R. Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters. J Biol Chem. 1987 May 5;262(13):6121–6127. [PubMed] [Google Scholar]
  29. Steadman R., Petersen M. M., Williams D., Matthews N., Williams J. D. The selective augmentation by recombinant human tumour necrosis factor-alpha of neutrophil responses to pathogenic Escherichia coli. Immunology. 1990 May;70(1):133–135. [PMC free article] [PubMed] [Google Scholar]
  30. Steadman R., Topley N., Jenner D. E., Davies M., Williams J. D. Type 1 fimbriate Escherichia coli stimulates a unique pattern of degranulation by human polymorphonuclear leukocytes. Infect Immun. 1988 Apr;56(4):815–822. doi: 10.1128/iai.56.4.815-822.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tsujimoto M., Yokota S., Vilcek J., Weissmann G. Tumor necrosis factor provokes superoxide anion generation from neutrophils. Biochem Biophys Res Commun. 1986 Jun 30;137(3):1094–1100. doi: 10.1016/0006-291x(86)90337-2. [DOI] [PubMed] [Google Scholar]
  32. Twomey B., Muid R. E., Dale M. M. The effect of putative protein kinase C inhibitors, K252a and staurosporine, on the human neutrophil respiratory burst activated by both receptor stimulation and post-receptor mechanisms. Br J Pharmacol. 1990 Aug;100(4):819–825. doi: 10.1111/j.1476-5381.1990.tb14098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Williams J. D., Robin J. L., Lewis R. A., Lee T. H., Austen K. F. Generation of leukotrienes by human monocytes pretreated with cytochalasin B and stimulated with formyl-methionyl-leucyl-phenylalanine. J Immunol. 1986 Jan;136(2):642–648. [PubMed] [Google Scholar]
  34. Wolfson M., McPhail L. C., Nasrallah V. N., Snyderman R. Phorbol myristate acetate mediates redistribution of protein kinase C in human neutrophils: potential role in the activation of the respiratory burst enzyme. J Immunol. 1985 Sep;135(3):2057–2062. [PubMed] [Google Scholar]
  35. Wright S. D., Meyer B. C. Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes. J Immunol. 1986 Mar 1;136(5):1759–1764. [PubMed] [Google Scholar]
  36. Yuo A., Kitagawa S., Suzuki I., Urabe A., Okabe T., Saito M., Takaku F. Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizing agonists. J Immunol. 1989 Mar 1;142(5):1678–1684. [PubMed] [Google Scholar]

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