Pharmacological intervention with oxidative burst in human neutrophils

Open access


In this study we investigated the effect of five therapeutically used drugs and four natural polyphenolic compounds on the mechanism of oxidative burst of human neutrophils concerning their participation in the generation of reactive oxygen species (ROS). The compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin > quercetin > curcumin > arbutin > dithiaden > carvedilol. The generation of intracellular reactive oxygen species in isolated neutrophils decreased in the same rank order, while carvedilol was ineffective. Scavenging of extracellular oxygen radicals followed the rank order of potency: N-feruloylserotonin > curcumin > quercetin > dithiaden. Arbutin and carvedilol had no effect. All compounds tested increased the activity of caspase-3 in cell-free system indicating a positive effect on apoptosis of neutrophils. Activation of protein kinase C was significantly decreased by dithiaden, curcumin, quercetin and N-feruloylserotonin. Carvedilol, dithiaden, quercetin and arbutin reduced activated neutrophil myeloperoxidase release more significantly compared with their less pronounced effect on superoxide generation The presented results are indicative of pharmacological intervention with neutrophils in pathological processes. Of particular interest was the effect of natural compounds. Intracellular inhibition of oxidative burst in isolated neutrophils by the drugs tested and natural antioxidants has to be further analysed since ROS play an important role in immunological responses of neutrophils.

Bjorkman L, Dahlgren C, Karlsson A, Brown KL, Bylun J. (2008). Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease. Arthr Rheumatism 58: 2931–2935.

Bylund J, Brown KL, Movitz C, Dahlgren C, Anna Karlsson A. (2010). Intracellular generation of superoxide by the phagocyte NADPH oxidase: How, where, and what for? Free Radical Biol Med 49: 1834–1835.

Cascao R, Rosário HS, Fonseca JE. (2009). Netrophils: warriors and commanders in immune mediated inflammatory diseases. Acta Reumatol Port 34: 313–26.

Drábiková K, Jančinová V, Nosáľ R, Solík P, Murín J, Holomáňová D. (2006). On the antioxidant activity of carvedilol in human polymorphonuclear leukocytes in vitro and ex vivo. Neuroendocrinol Lett 27: 138 –140.

Drábikova K, Jančinová V, Nosáľ R, Pečivová J, Mačičková T, Turčáni P. (2007). Inhibitory effect of stobadine on FMLP-induced chemiluminescence in human whole blood and isolated polymorphonuclear leukocytes. Luminescence 22: 67–71.

Drábiková K, Perečko T, Nosáľ R, Bauerová K, Poništ S, Mihálová D, Kogan G, Jančinová V. (2009). Glucomanan reduces neutrophil free radical production in vitro and in rats with adjuvant arthritis. Pharmacol Res 59: 399–403.

Droge W. (2002). Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95.

Fialkow L, Wang Y, Downey GP. (2007). Reactive oxygen and nitrogen species as signalling molecules regulating neutrophil functions. Free Rad Biol Med 42: 153–64.

Hallet JM, Leitch AE, Riley NA, Duffin R, Haslett C, Rossi AG. (2008). Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the resolution of inflammation. Trends Pharmacol Sci 29: 250–257.

Halliwell B, Whiteman M. (2004). Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Brit J Pharmacol 142: 231–255.

Harmatha J, Budešínský M, Vokáč K, Pavlík M, Gruner K, Laudová V. (2007). Lignan glucosides and serotonin phenyl propanoids from the seeds of Leuzea carthamoides. Coll Czechoslov Chem Commun 72: 334–346.

Holmdahl R, Sareila O, Olsson LM, Backdahl L, Wing K. (2016). Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. Immunol Rev 2016: 228–247.

Jančinová V, Drábiková K, Nosáľ R, Holomáňová D. (2006a). Extra- and intra-cellular formation of reactive oxygen species by human neutrophils in the presence of pheniramine, chlorpheniramine and brompheniramine. Neuro Endocrinol Lett 27: 141–143.

Jančinová V, Drábiková K, Nosáľ R, Račková L, Májeková M, Holomáňová D. (2006b). The combined luminol-isoluminol chemiluminescence method for differentiation between extracellular and intracellular oxidant production by neutrophils. Redox Rep 11: 110–116.

Jančinová V, Petríková M, Perečko T, Drábiková K, Nosáľ R, Bauerová K. (2007). Inhibition of neutrophil oxidative burst with arbutin.. Effects in vitro and in adjuvant arthritis. Chem Listy 101: 189–191.

Jančinová V, Perečko T, Nosáľ R, Košťálová D, Baueroá K, Drábiková K. (2009). Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition. Eur J Pharmacol 612: 161–166.

Jančinová V, Perečko T, Nosáľ R, Mihalová D, Bauerová K, Drábiková K. (2011). Pharmacological regulation of neutrophil activity and apoptosis. Contribution to new strategy for modulation of inflammatory processes. Interdiscip Toxicol 4: 11–14.

Jančinová V, Perečko T, Harmatha J, Nosáľ R, Drábiková K. (2012a). Decreased activity and accelerated apoptosis of neutrophils in the presence of natural polyphenols. Interdiscip Toxicol 5: 59–64.

Jančinová V, Perečko T, Nosáľ R, Harmatha J, Šmidrkal J, Drábiková K. (2012b). The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis. Acta Pharmacol Sin 33: 1285–1292.

Jančinová V, Pažoureková S, Lucová M, Perečko T, Mihalová D, Bauerová K, Nosáľ R, Drábiková K. (2015). Selective inhibition of extracellular oxidants liberated from human neutrophils. A new mechanism potentially involved in the antiinflammatory activity of hydroxychloroquine. Int Immunopharmacol 28: 175–181.

Klink M, Jastrembska K, Bednarska K, Banasik M, Sulowska Z. (2009). Effect of nitric oxide donors on NADPH oxidase signaling pathway in human neutrophils in vitro. Immunobiology 214: 692–702.

Lonkar P, Dedon PC. (2011). Reactive species and DNA damage in chronic inflammation: reconciling chemical mechanisms and biological fates. Int J Cancer 128: 1999–2009.

Nosáľ R, Drábiková K, Jančinová V, Mačičková T, Pečivová J, Perečko T, Harmatha J. (2015). Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes. Gen Physiol Biophys 34: 209–216.

Nosáľ R, Drábiková K, Jančinová V, Mačičková T, Pečivová J, Perečko T, Harmatha J, Šmidrkal J. (2015). On the pharmacology of oxidative burst of human neutrophils. Physiol Res 64: S445–S452.

Nosáľ R, Perečko T, Jančinová V, Drábiková K, Harmatha J, Sviteková K. (2011). Naturally appearing N-feruloylserotonin isomers suppress oxidative burst of human neutrophils at the protein kinase C level. Pharmacol Rep 63: 790–798.

Nosáľ R, Drábiková K, Jančinová V, Moravcová J, Lojek A, Číž M, Mačičková T, Pečivová J. (2009). H1-antihistamines and oxidative burst of professional phagocytes. Neuroendocrinol. Lett. 30: 133–136.

Nosáľ R, Drábiková K, Jančinová V, Perečko T, Ambrožová G, Číž M, Lojek A, Pekarová M, Šmidrkal J, Harmatha J. (2014). On the molecular pharmacology of resveratrol on oxidative burst inhibition in professional phagocytes. Oxid Med Cell Longev 2014(706269): 9 pages.

O’Dowd YM, El-Benna J, Perianin A, Newsholme P. (2004). Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst in human neutrophils by adrenaline: inhibition of phospholipase A2 activity but not p47phox phosphorylation and translocation. Biochem Pharmacol 67: 183–190.

Pan MH,Chang ZH, Badmaev V, Nagabhushanam K, CňHo CT. (2007). Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. J Agricult Food Chem 55: 7777–85.

Pan MH, Chiou YS, Chen WJ, Wang JM, Badmaev V, Ho CT. (2009). Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis 30: 1234–42.

Pečivová J, Mačičková T, Lojek A, Gallová L, Číž M, Nosáľ R, Holomáňová D. (2007). In vitro effect of carvedilol on professional phagocytes. Pharmacol 79: 86–92.

Perečko T, Jančinová V, Drábiková K, Nosáľ R, Harmatha J. (2008). Structure efficiency relationship in derivatives of stilbene. Comparison of resveratrol, pinosylvin and pterostilbene. Neuroendocrinol Lett 29: 802–805.

Perečko T, Drábiková K, Račková L, Číž M, Podborský M, Lojek A, Harmatha J, Šmidrkal J, Nosáľ R, Jančinová V. (2010). Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoposis in human neutrophils in vitro. Neuroendocrinol Lett 31: 84–90.

Raad H, Paclet MH,Boussetta T, Kroviarski Y, Morel F, Quinn MT, Gougerot Pocidalo MA, Dang PM, El Benna J. (2009). Regulation of the phagocyte NADPH oxidase activity: phosphorylation of gp91phox/NOX2 by protein kinase C e nhances its diaphorase activity and binding to Rac2, p67phox, and p47phox. FASEB J 23: 1011–1022.

Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K. (2014). Oxidative stress, prooxidants, and antioxidants. BioMed Research International 2014(761264): 19 pages.

Wright HL, Moots RJ, Bucknall RC, Edwards SW. (2010) Neutrophil function in inflammation and inflammatory diseases. Rheumatology 49: 1618–31.

Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

Journal Information

CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 503 361 24
PDF Downloads 138 109 12