Skip to main content

Advertisement

Log in

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

  • Brief Communication
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. World Health Organization (2001) Global prevalence and incidence of selected curable sexually transmitted infections. Overview and estimates. World Health Organization, Geneva

    Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  3. Goldstein F, Goldman MB, Cramer DW (1993) Relation of tubal infertility to a story of sexually transmitted diseases. Am J Epidemiol 137:577–584

    Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  8. Petrin D, Delgaty K, Bhatt R, Garber G (1998) Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 11:300–317

    PubMed  CAS  Google Scholar 

  9. Lehker MW, Alderete JF (2000) Biology of trichomonosis. Curr Opin Infect Dis 13:37–45

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 63:3864–3870

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  15. Shaio MF, Lin PR, Lee CS, Hou SC, Tang P, Yanga KD (1992) Novel neutrophil-activating factor released by Trichomonas vaginalis. Infect Immun 60:4475–4482

    PubMed  CAS  Google Scholar 

  16. Shaio MF, Lin PR (1995) Leukotriene B4 levels in the vaginal discharges from cases of trichomoniasis. Ann Trop Med Parasitol 89:85–88

    PubMed  CAS  Google Scholar 

  17. Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197. doi:10.1038/ni1276

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  19. Salmi M, Jalkanen S (2005) Cell-surface enzymes in control of leukocyte trafficking. Nat Rev Immunol 5:760–771. doi:10.1038/nri1705

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  21. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797. doi:10.1152/physrev.00043.2006

    Article  PubMed  CAS  Google Scholar 

  22. Zimmermann H (2001) Ectonucleotidases: some recent developments and a note on nomenclature. Drug Develop Res 52:44–56. doi:10.1002/ddr.1097

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  27. Diamond LS (1957) The establishment of various Trichomonas of animals and man in axenic cultures. J Parasitol 43:488–490

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 97:77–89

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  32. Junger GW (2008) Purinergic regulation of neutrophil chemotaxis. Cell Mol Life Sci 65:2528–2540. doi:10.1007/s00018-008-8095-1

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  39. Coleman J (2001) Nitric oxide in immunity and inflammation. Int Immunopharmacol 1:1397–1406. doi:10.1016/S1567-5769(01)00086-8

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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 71:367–377

    PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tiana Tasca.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frasson, A.P., De Carli, G.A., Bonan, C.D. et al. Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis . Purinergic Signalling 8, 1–9 (2012). https://doi.org/10.1007/s11302-011-9254-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-011-9254-7

Keywords

Navigation