title: Nitric oxide produced in the lungs of mice immunized with the radiation-attenuated schistosome vaccine is not the major agent causing challenge parasite elimination.
abstract: Mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni exhibit high levels of protection against a challenge with normal larvae. The immune effector mechanism, which operates against schistosomula in the lungs, requires CD4+ T cells capable of producing interferon-gamma (IFN-gamma). This cytokine can stimulate production of nitric oxide (NO), via its ability to up-regulate inducible nitric oxide synthase (iNOS). We have therefore evaluated the potential role of NO in the effector mechanism operating in vaccinated mice. Evidence for the production of NO in the lungs of such animals was obtained from assays on antigen-stimulated airway cell cultures. Enhanced levels of NO, compared with those in cultures from control mice, were detected both after vaccination and after challenge; elevated levels of iNOS mRNA were also present in whole lung after challenge. However, administration of an iNOS inhibitor to vaccinated mice after percutaneous challenge did not significantly increase the worm burden. Furthermore, when mice with a disrupted iNOS gene were vaccinated they showed a highly significant level of protection. Although NO from activated macrophages can mediate cytotoxic killing of newly transformed schistosomula in vitro, we have demonstrated that the addition of erythrocytes to these larvicidal assays abolishes its effects. We interpret this to mean that once migrating schistosomula enter the bloodstream they will be protected against the cytotoxic actions of NO. Our data thus provide little evidence to implicate NO as a major component of the pulmonary effector response to S. mansoni in vaccinated mice.
authors.affiliation: Department of Biology, University of York, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Coulson
authors.forename: L E
authors.initials: LE
authors.lastname: Smythies
authors.forename: C
authors.initials: C
authors.lastname: Betts
authors.forename: N A
authors.initials: NA
authors.lastname: Mabbott
authors.forename: J M
authors.initials: JM
authors.lastname: Sternberg
authors.forename: X G
authors.initials: XG
authors.lastname: Wei
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
authors.forename: R A
authors.initials: RA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D015870:Gene Expression; D008168:Lung / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014613:Vaccines, Attenuated; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse