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Purinergic Signalling

, Volume 8, Issue 1, pp 1–9 | Cite as

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

  • Amanda Piccoli Frasson
  • Geraldo Attilio De Carli
  • Carla Denise Bonan
  • Tiana TascaEmail author
Brief Communication

Abstract

Trichomonas vaginalis is a parasite from the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. The neutrophil infiltration has been considered to be primarily responsible for cytological changes observed at infection site, and the chemoattractants can play an important role in this leukocytic recruitment. Nitric oxide (NO) is one of the most widespread mediator compounds, and it is implicated in modulation of immunological mechanisms. Extracellular nucleotides and nucleosides are signaling molecules involved in several processes, including immune responses and control of leukocyte trafficking. Ectonucleoside triphosphate diphosphohydrolase members, ecto-5′-nucleotidase, and adenosine deaminase (ectoADA) have been characterized in T. vaginalis. Herein, we investigated the effects of purinergic system on NO production by neutrophils stimulated with T. vaginalis. The trophozoites were able to induce a high NO synthesis by neutrophils through iNOS pathway. The extracellular nucleotides ATP, ADP, and ATPγS (a non-hydrolyzable ATP analog) showed no significant change in NO secretion. In contrast, adenosine and its degradation product, inosine, promoted a low production of the compound. The immunosuppressive effect of adenosine upon NO release by neutrophils occurred due to adenosine A2A receptor activation. The ecto-5′-nucleotidase activity displayed by T. vaginalis was shown to be important in adenosine generation, indicating the efficiency of purinergic cascade. Our data suggest the influence of purinergic signaling, specifically adenosinergic system, on NO production by neutrophils in T. vaginalis infection, contributing to the immunological aspects of disease.

Keywords

Trichomonas vaginalis Neutrophils Nitric oxide Purinergic signaling Ectonucleotidases Adenosine 

Notes

Acknowledgements

A.P.F. is recipient of fellowship from CNPq. This study received financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) grant #477348/2008-4 awarded to T.T., and from the NANOBIOTEC-Brazil program from CAPES (Brazil). The authors thank Dr. Christina Bittar and Hospital de Clínicas de Porto Alegre for neutrophil phenotypic analysis.

References

  1. 1.
    World Health Organization (2001) Global prevalence and incidence of selected curable sexually transmitted infections. Overview and estimates. World Health Organization, GenevaGoogle Scholar
  2. 2.
    Cotch MF, Pastorek JG, Nugent RP, Hillier SL, Gibbs RS, Martin DH, Eschenbach DA, Edelman R, Carey JC, Regan JA, Krohn MA, Klebanoff MA, Rao AV, Rhoads GG (1997) The vaginal infections and prematurity study group. Sex Transm Dis 24:353–360. doi: 10.1097/00007435-199707000-00008 PubMedCrossRefGoogle Scholar
  3. 3.
    Goldstein F, Goldman MB, Cramer DW (1993) Relation of tubal infertility to a story of sexually transmitted diseases. Am J Epidemiol 137:577–584Google Scholar
  4. 4.
    Viikki M, Pukkala E, Nieminen P, Hakama M (2000) Gynaecological infections as risk determinants of subsequent cervical neoplasia. Acta Oncol (Madr) 39:71–75. doi: 10.1080/028418600431003 CrossRefGoogle Scholar
  5. 5.
    Cherpes T, Wiesenfeld H, Melan M, Kant JA, Consentino LA, Meyn LA, Hillier SL (2006) The associations between pelvic inflammatory disease, Trichomonas vaginalis infection, and positive herpes simplex virus type 2 serology. Sex Transm Dis 33:747–752. doi: 10.1097/01.olq.0000218869.52753.c7 PubMedCrossRefGoogle Scholar
  6. 6.
    Johnston VJ, Mabey DC (2008) Global epidemiology and control of Trichomonas vaginalis. Curr Opin Infect Dis 21:56–64. doi: 10.1097/QCO.0b013e3282f3d999 PubMedCrossRefGoogle Scholar
  7. 7.
    Van Der Pol B, Kwok C, Pierre-Louis B, Rinaldi A, Salata RA, Chen PL, Van De Wijgert J, Miro F, Mugerwa R, Chipato T, Morrison CS (2008) Trichomonas vaginalis infection and human immunodeficiency virus acquisition in African women. J Infect Dis 197:548–554. doi: 10.1086/526496 CrossRefGoogle Scholar
  8. 8.
    Petrin D, Delgaty K, Bhatt R, Garber G (1998) Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 11:300–317PubMedGoogle Scholar
  9. 9.
    Lehker MW, Alderete JF (2000) Biology of trichomonosis. Curr Opin Infect Dis 13:37–45PubMedCrossRefGoogle Scholar
  10. 10.
    Fichorova RN (2009) Impact of T. vaginalis infection on innate immune responses and reproductive outcome. J Reprod Immunol 83:185–189. doi: 10.1016/j.jri.2009.08.007 PubMedCrossRefGoogle Scholar
  11. 11.
    Escario A, Gómez Barrio A, Simons Diez B, Escario JA (2010) Immunohistochemical study of the vaginal inflammatory response in experimental trichomoniasis. Acta Trop 114:22–30. doi: 10.1016/j.actatropica.2009.12.002 PubMedCrossRefGoogle Scholar
  12. 12.
    Ryu JS, Kang JH, Jung SY, Shin MH, Kim JM, Park H, Min DY (2004) Production of interleukin-8 by human neutrophils stimulated with Trichomonas vaginalis. Infect Immun 72:1326–1332. doi: 10.1128/IAI.72.3.1326-1332.2004 PubMedCrossRefGoogle Scholar
  13. 13.
    Shaio MF, Lin PR, Liu JY, Yang KD (1995) Generation of interleukin-8 from human monocytes in response to Trichomonas vaginalis stimulation. Infect Immun 63:3864–3870PubMedGoogle Scholar
  14. 14.
    Park GC, Ryu JS, Min DY (1997) The role of nitric oxide as an effector of macrophage-mediated cytotoxicity against Trichomonas vaginalis. Korean J Parasitol 35:189–195. doi: 10.3347/kjp.1997.35.3.189 PubMedCrossRefGoogle Scholar
  15. 15.
    Shaio MF, Lin PR, Lee CS, Hou SC, Tang P, Yanga KD (1992) Novel neutrophil-activating factor released by Trichomonas vaginalis. Infect Immun 60:4475–4482PubMedGoogle Scholar
  16. 16.
    Shaio MF, Lin PR (1995) Leukotriene B4 levels in the vaginal discharges from cases of trichomoniasis. Ann Trop Med Parasitol 89:85–88PubMedGoogle Scholar
  17. 17.
    Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197. doi: 10.1038/ni1276 PubMedCrossRefGoogle Scholar
  18. 18.
    Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783:673–694. doi: 10.1016/j.bbamcr.2008.01.024 PubMedCrossRefGoogle Scholar
  19. 19.
    Salmi M, Jalkanen S (2005) Cell-surface enzymes in control of leukocyte trafficking. Nat Rev Immunol 5:760–771. doi: 10.1038/nri1705 PubMedCrossRefGoogle Scholar
  20. 20.
    Bours MJL, Swennen ELR, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Therapeut 112:358–404. doi: 10.1016/j.pharmthera.2005.04.013 CrossRefGoogle Scholar
  21. 21.
    Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797. doi: 10.1152/physrev.00043.2006 PubMedCrossRefGoogle Scholar
  22. 22.
    Zimmermann H (2001) Ectonucleotidases: some recent developments and a note on nomenclature. Drug Develop Res 52:44–56. doi: 10.1002/ddr.1097 CrossRefGoogle Scholar
  23. 23.
    Robson SC, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430. doi: 10.1007/s11302-006-9003-5 PubMedCrossRefGoogle Scholar
  24. 24.
    Matos JAA, Borges FP, Tasca T, Bogo MR, De Carli GA, Fauth MG, Dias RD, Bonan CD (2001) Characterization of an ATP diphosphohydrolase (Apyrase, EC 3.6.1.5) activity in Trichomonas vaginalis. Int J Parasitol 31:770–775. doi: 10.1016/S0020-7519(01)00191-6 CrossRefGoogle Scholar
  25. 25.
    Tasca T, Bonan CD, De Carli GA, Battastini AMO, Sarkis JJF (2003) Characterization of an ecto-5′-nucleotidase (EC 3.1.3.5) activity in intact cells of Trichomonas vaginalis. Exp Parasitol 105:167–173. doi: 10.1016/j.exppara.2003.12.001 PubMedCrossRefGoogle Scholar
  26. 26.
    Weizenmann M, Frasson AP, de Barros MP, Vieira Pde B, Rosemberg DB, De Carli GA, Bogo MR, Bonan CD, Tasca T (2011) Kinetic characterization and gene expression of adenosine deaminase in intact trophozoites of Trichomonas vaginalis. FEMS Microbiol Lett 319:115–124. doi: 10.1111/j.1574-6968.2011.02283.x PubMedCrossRefGoogle Scholar
  27. 27.
    Diamond LS (1957) The establishment of various Trichomonas of animals and man in axenic cultures. J Parasitol 43:488–490PubMedCrossRefGoogle Scholar
  28. 28.
    Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:218–254. doi: 10.1016/0003-2697(76)90527-3 CrossRefGoogle Scholar
  29. 29.
    Chan KM, Delfert D, Junger KD (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375–380. doi: 10.1016/0003-2697(86)90640-8 PubMedCrossRefGoogle Scholar
  30. 30.
    Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 97:77–89PubMedGoogle Scholar
  31. 31.
    Di Virgilio F (2007) Purinergic signalling in the immune system. A brief update. Purinergic Signal 3:1–3. doi: 10.1007/s11302-006-9048-5 PubMedCrossRefGoogle Scholar
  32. 32.
    Junger GW (2008) Purinergic regulation of neutrophil chemotaxis. Cell Mol Life Sci 65:2528–2540. doi: 10.1007/s00018-008-8095-1 PubMedCrossRefGoogle Scholar
  33. 33.
    Chen Y, Yao Y, Sumi Y, Li A, To UK, Elkhal A, Inoue Y, Woehrle T, Zhang Q, Hauser C, Junger WG (2010) Purinergic signaling: a fundamental mechanism in neutrophil activation. Sci Signal 125:ra45. doi: 10.1126/scisignal.2000549 CrossRefGoogle Scholar
  34. 34.
    Armstrong R (2001) The physiological role and pharmacological potential of nitric oxide in neutrophil activation. Int Immunopharmacol 1:1501–1512. doi: 10.1016/S1567-5769(01)00094-7 PubMedCrossRefGoogle Scholar
  35. 35.
    Wink DA, Mitchell JB (1998) Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 25:434–456. doi: 10.1016/S0891-5849(98)00092-6 PubMedCrossRefGoogle Scholar
  36. 36.
    Zagryazhskaya NA, Lindner SC, Grishina ZV, Galkina SI, Steinhilber D, Sud'ina GF (2010) Nitric oxide mediates distinct effects of various LPS chemotypes on phagocytosis and leukotriene synthesis in human neutrophils. Int J Biochem Cell Biol 42:921–931. doi: 10.1016/j.biocel.2010.01.025 PubMedCrossRefGoogle Scholar
  37. 37.
    Han IH, Goo SY, Park SJ, Hwang SJ, Kim YS, Yang MS, Ahn MH, Ryu JS (2009) Proinflammatory cytokine and nitric oxide production by human macrophages stimulated with Trichomonas vaginalis. Korean J Parasitol 47:205–212. doi: 10.3347/kjp.2009.47.3.205 PubMedCrossRefGoogle Scholar
  38. 38.
    Malla N, Yadav M, Gupta I (2007) Kinetics of serum and local cytokine profile in experimental intravaginal trichomoniasis induced with Trichomonas vaginalis isolates from symptomatic and asymptomatic women. Parasite Immunol 29:101–105. doi: 10.1111/j.1365-3024.2006.00914.x PubMedCrossRefGoogle Scholar
  39. 39.
    Coleman J (2001) Nitric oxide in immunity and inflammation. Int Immunopharmacol 1:1397–1406. doi: 10.1016/S1567-5769(01)00086-8 PubMedCrossRefGoogle Scholar
  40. 40.
    Pulte ED, Broekman MJ, Olson KE, Drosopoulos JHF, Kizer JR, Islam N, Marcus AJ (2007) CD39/NTPDase-1 activity and expression in normal leukocytes. Thromb Res 121:309–317. doi: 10.1016/j.thromres.2007.04.008 PubMedCrossRefGoogle Scholar
  41. 41.
    Lévesque SA, Lavoie EG, Lecka J, Bigonnesse F, Sévigny J (2007) Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases. Br J Pharmacol 152:141–150. doi: 10.1038/sj.bjp.0707361 PubMedCrossRefGoogle Scholar
  42. 42.
    Sansom FM, Robson SC, Hartland EL (2008) Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host–pathogen interactions. Microbiol Mol Biol Rev 72:765–781. doi: 10.1128/MMBR.00013-08 PubMedCrossRefGoogle Scholar
  43. 43.
    Alderete JF, Millsap KW, Lehker MW, Benchimol M (2001) Enzymes on microbial pathogens and Trichomonas vaginalis: molecular mimicry and functional diversity. Cell Microbiol 3:359–370. doi: 10.1046/j.1462-5822.2001.00126.x PubMedCrossRefGoogle Scholar
  44. 44.
    Tasca T, Bonan CD, De Carli GA, Sarkis JJ, Alderete JF (2005) Heterogeneity in extracellular nucleotide hydrolysis among clinical isolates of Trichomonas vaginalis. Parasitology 131:71–78. doi: 10.1017/S0031182005007377 PubMedCrossRefGoogle Scholar
  45. 45.
    Haskó G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25:33–39. doi: 10.1016/j.it.2003.11.003 PubMedCrossRefGoogle Scholar
  46. 46.
    Haskó G, Sitkovsky MV, Szabó C (2004) Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci 25:152–157. doi: 10.1016/j.tips.2004.01.006 PubMedCrossRefGoogle Scholar
  47. 47.
    Heyworth PG, Gutteridge WE, Ginger CD (1982) Purine metabolism in Trichomonas vaginalis. FEBS Lett 141:106–110. doi: 10.1016/0014-5793(82)80026-4 PubMedCrossRefGoogle Scholar
  48. 48.
    Heyworth PG, Gutteridge WE, Ginger CD (1984) Pyrimidine metabolism in Trichomonas vaginalis. FEBS Lett 176:55–60. doi: 10.1016/0014-5793(84)80910-2 PubMedCrossRefGoogle Scholar
  49. 49.
    Fortin A, Harbour D, Fernandes M, Borgeat P, Bourgoin S (2006) Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide. J Leukoc Biol 79:574–585. doi: 10.1189/jlb.0505249 PubMedCrossRefGoogle Scholar
  50. 50.
    Thibault N, Burelout C, Harbour D, Borgeat P, Naccache PH, Bourgoin SG (2002) Occupancy of adenosine A2A receptors promotes fMLP-induced cyclic AMP accumulation in human neutrophils: impact on phospholipase D activity and recruitment of small GTPases to membranes. J Leukoc Biol 71:367–377PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Amanda Piccoli Frasson
    • 1
  • Geraldo Attilio De Carli
    • 2
  • Carla Denise Bonan
    • 3
  • Tiana Tasca
    • 1
    Email author
  1. 1.Laboratório de Pesquisa em Parasitologia, Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Instituto de Geriatria e GerontologiaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  3. 3.Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de BiociênciasPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil

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