Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 343, Issue 4, pp 370–376 | Cite as

Differential inhibition and potentiation of chemoattractant-induced superoxide formation in human neutrophils by the cell-permeant analogue of cyclic GMP, N2,2′-O-dibutyryl guanosine 3′:5′-cyclic monophosphate

  • Jürgen Ervens
  • Günter Schultz
  • Roland Seifert
Article

Summary

Human neutrophils possess a superoxide (O inf2 sup− )-forming NADPH oxidase which is activated by the chemoattractants, N-formyl-l-methionyl-l-leucyl-l,-phenylalanine (fMet-Leu-Phe), complement C5a, platelet-activating factor and leukotriene B4. We studied the roles of cAMP and cGMP in the regulation of O inf2 sup− formation using the cell-permeant analogues of cyclic nucleotides, N6,2′-O-dibutyryl adenosine 3′:5′-cyclic monophosphate (Bt2cAMP) and N2,2′-O-dibutyryl guanosine 3′:5′-cyclic monophosphate (Bt2cGMP). Bt2cAMP inhibited O inf2 sup− formation induced by these chemoattractants to similar extents. Bt2cGMP as low as 10 μmol/l significantly inhibited O inf2 sup− formation induced by fMet-Leu-Phe at a submaximally effective concentration (50 nmol/1), and Bt2cGMP was more effective in diminishing O inf2 sup− formation than Bt2cAMP. In contrast, Bt2cGMP did not affect O inf2 sup− formation induced by fMet-Leu-Phe at a maximally effective concentration (1 μmol/l). Bt2cGMP (0.1 and 1 mmol/l) enhanced O inf2 sup− formation induced by 0.1 μmol/l C5a by 23% and 49%, respectively, and Bt2cGMP antagonized inhibition of O inf2 sup− formation caused by Bt2cAMP. Bt2cGMP inhibited platelet-activating factor-induced O inf2 sup− formation to a lesser extent than Bt2cAMP and had no effect on that induced by leukotriene B4. Bt2cAMP and Bt2cGMP had no effect on O inf2 sup− formation induced by NaF, γ-hexachlorocyclohexane, phorbol myristate acetate, A 23187 and arachidonic acid. Our data suggest that: 1. Bt2cAMP generally inhibits chemoattractant-stimulated O inf2 sup− formation. 2. Bt2cGMP inhibits fMet-Leu-Phe- and platelet-activating factor-stimulated O inf2 sup− formation but potentiates C5a-induced O inf2 sup− formation. 3. The lack of effect of cyclic nucleotides on O inf2 sup− formation induced by agents other than receptor agonists indicates that cAMP and cGMP modulate early steps of the signal transduction processes initiated by chemoattractants.

Key words

N6,2′-O-dibutyryl adenosine 3′:5′-cyclic monophosphate N2,2′-O-dibutyryl guanosine 3′:5′ 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beavo JA (1988) Multiple isozymes of cyclic nucleotide phosphodiesterase. Adv Second Messenger Phosphoprotein Res 22:1–38PubMedGoogle Scholar
  2. Bender JG, van Epps DE, Chenoweth DE (1987) Independent regulation of human neutrophil chemotactic receptors after activation. J Immunol 139:3028–3033PubMedGoogle Scholar
  3. Böhme E, Graf H, Schultz G (1978) Effects of sodium nitroprusside and other smooth muscle relaxants on cyclic GMP formation in smooth muscle and platelets. Adv Cycl Nucl Res 9:131–143Google Scholar
  4. Boss GR (1989) cGMP-induced differentiation of the promyelocytic cell line HL-60. Proc Natl Acad Sci USA 86:7174–7178CrossRefGoogle Scholar
  5. Burde R, Seifert R, Buschauer A, Schultz G (1989) Histamine inhibits activation of human neutrophils and HL-60 leukemic cells via H2-receptors. Naunyn-Schmiedeberg's Arch Pharmacol 340:671–678CrossRefGoogle Scholar
  6. Ignarro LJ, George WJ (1974) Hormonal control of lysosomal enzyme release from human neutrophils: Elevation of cyclic nucleotide levels by autonomic neurohormones. Proc Natl Acad Sci USA 71:2027–2031CrossRefGoogle Scholar
  7. Jesaitis AJ, Tolley JO, Allen RA (1986) Receptor-cytoskeleton interactions and membrane traffic may regulate chemoattractant-induced superoxide production in human granulocytes. J Biol Chem 261:13662–13669PubMedGoogle Scholar
  8. Kaplan SS, Billiar T, Zdziarski UE, Simmons RL, Basford RE (1989) Inhibition of chemotaxis with NG-monomethyl-l-arginine: A role for cyclic GMP. Blood 74:1885–1887PubMedGoogle Scholar
  9. Kim U-H, Kim JW, Rhee SG (1989) Phosphorylation of phospholipase C-y by cAMP-dependent protein kinase. J Biol Chem 264:20167–20170PubMedGoogle Scholar
  10. Kramer IM, van der Bend RL, Verhoeven AJ, Roos D (1988) The 47-kDa protein involved in the NADPH:O2 oxidoreductase activity of human neutrophils is phosphorylated by cyclic AMP-dependent protein kinase without induction of a respiratory burst. Biochim Biophys Acta 971:189–196PubMedGoogle Scholar
  11. Kuo JF, Shoji M, Kuo W-N (1978) Molecular and physiopathologic aspects of mammalian cyclic GMP-dependent protein kinase. Annu Rev Pharmacol Toxicol 18:341–355CrossRefGoogle Scholar
  12. Lad PM, Glovsky MM, Richards JH, Smiley PA, Backstrom B (1985) Regulation of human neutrophil guanylate cyclase by metal ions, free radicals and the muscarinic cholinergic receptor. Mol Immunol 22:731–739CrossRefGoogle Scholar
  13. Lefkowitz RJ, Caron MC (1986) Regulation of adrenergic receptor function by phosphorylation. Curr Top Cell Regul 28:209–231CrossRefGoogle Scholar
  14. Malech HL, Gallin MD (1987) Neutrophils in human diseases. N Engl J Med 317:687–694CrossRefGoogle Scholar
  15. McPhail LC, Clayton CC, Snyderman R (1984) The NADPH oxidase of human polymorphonuclear leucocytes. Evidence for regulation by multiple signals. J Biol Chem 259:5768–5775PubMedGoogle Scholar
  16. Misaki N, Imaizumi T, Watanabe Y (1989) Cyclic AMP-dependent protein kinase interferes with GTPTS stimulated IP3 formation in differentiated HL-60 cell membranes. Life Sci 45:1671–1678CrossRefGoogle Scholar
  17. Moncada S, Palmer RMJ, Higgs EA (1989) Biosynthesis of nitric oxide from l-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715CrossRefGoogle Scholar
  18. Mueller H, Sklar LA (1989) Coupling of antagonistic signalling pathways in modulation of neutrophil function. J Cell Biochem 40:287–294CrossRefGoogle Scholar
  19. Naor Z (1990) Cyclic GMP stimulates inositol phosphate production in cultured pituitary cells: Possible implication to signal transduction. Biochem Biophys Res Commun 167:982–992CrossRefGoogle Scholar
  20. Pryzwansky KB, Wyatt TA, Nichols H, Lincoln TM (1990) Compartmentalization of cyclic GMP-dependent protein kinase in formyl-peptide stimulated neutrophils. Blood 76:612–618PubMedGoogle Scholar
  21. Rossi F (1986) The O2-forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta 853:65–89CrossRefGoogle Scholar
  22. Schmidt HHHW, Seifert R, Böhme E (1989) Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4. FEBS Lett 244:357–360CrossRefGoogle Scholar
  23. Schröder H, Ney P, Woditsch I, Schrör K (1990) Cyclic GMP mediates SIN-1-induced inhibition of human polymorphonuclear leukocytes. Eur J Pharmacol 182:211–218CrossRefGoogle Scholar
  24. Schultz K-D, Böhme E, Kreye VAW, Schultz G (1979) Relaxation of hormonally stimulated smooth muscular tissues by the 8-bromo derivative of cyclic GMP. Naunyn-Schmiedeberg's Arch Pharmacol 306:1–9CrossRefGoogle Scholar
  25. Seifert R, Schultz G (1991) The superoxide-forming NADPH oxidase of phagocytes: An enzyme system regulated by multiple mechanisms. Rev Physiol Biochem Pharmacol (in press)Google Scholar
  26. Seifert R, Burde R, Schultz G (1989a) Activation of NADPH oxidase by purine and pyrimidine nucleotides involves G proteins and is potentiated by chemotactic peptides. Biochem J 259:813–819CrossRefGoogle Scholar
  27. Seifert R, Burde R, Schultz G (1989b) Lack of effect of opioid peptides, morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells. Naunyn-Schmiedeberg's Arch Pharmacol 340:101–106CrossRefGoogle Scholar
  28. Seifert R, Wenzel K, Eckstein F, Schultz G (1989c) Purine and pyrimidine nucleotides potentiate activation of NADPH oxidase and degranulation by chemotactic peptides and induce aggregation of human neutrophils via G proteins. Eur J Biochem 181:277–285CrossRefGoogle Scholar
  29. Seifert R, Jungblut P, Schultz G (1989d) Differential expression of cytosolic activation factors for NADPH oxidase in HL-60 leukemic cells. Biochem Biophys Res Commun 161:1109–1117CrossRefGoogle Scholar
  30. Tremblay J, Gerzer R, Hamet P (1988) Cyclic GMP in cell function. Adv Second Messenger Phosphoprotein Res 22:319–383PubMedGoogle Scholar
  31. Waldman SA, Murad F (1987) Cyclic GMP synthesis and function. Pharmacol Rev 39:163–196PubMedGoogle Scholar
  32. Walter U (1989) Physiological role of cGMP and cGMP-dependent protein kinase in the cardiovascular system. Rev Physiol Biochem Pharmacol 113:41–88CrossRefGoogle Scholar
  33. Wright CD, Mülsch A, Busse R, Osswald H (1989) Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun 160:813–819CrossRefGoogle Scholar
  34. Wymann MP, von Tscharner V, Daranleau DA, Baggiolini M (1987) The onset of the respiratory burst in human neutrophils. Real-time studies of H2O2 formation reveal a rapid agonist-induced transduction process. J Biol Chem 262:12048–12053PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Jürgen Ervens
    • 1
  • Günter Schultz
    • 1
  • Roland Seifert
    • 1
  1. 1.Institut für PharmakologieFreie Universität BerlinBerlin 33Germany

Personalised recommendations