Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis
- 118 Downloads
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.
KeywordsTrichomonas vaginalis Neutrophils Nitric oxide Purinergic signaling Ectonucleotidases Adenosine
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.
- 1.World Health Organization (2001) Global prevalence and incidence of selected curable sexually transmitted infections. Overview and estimates. World Health Organization, GenevaGoogle 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 PubMedCrossRefGoogle Scholar
- 3.Goldstein F, Goldman MB, Cramer DW (1993) Relation of tubal infertility to a story of sexually transmitted diseases. Am J Epidemiol 137:577–584Google 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 PubMedCrossRefGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 71:367–377PubMedGoogle Scholar