Nitric oxide produced in the lungs of mice immunized with the radiation-attenuate schistosome vaccine is not the major agent causing challenge parasite elimination

P S Coulson, L E Smythies, C Betts, N A Mabbott, Jeremy M Sternberg, X G Wei, F Y Liew, R A Wilson

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 defected 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.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalImmunology
Volume93
Issue number1
DOIs
Publication statusPublished - Jan 1998

Keywords

  • INTERFERON-GAMMA RECEPTOR
  • IRRADIATED CERCARIAE
  • PULMONARY RESPONSES
  • TRYPANOSOMA-BRUCEI
  • CYTO-TOXICITY
  • L-ARGININE
  • T-CELL
  • MANSONI
  • MACROPHAGES
  • RESISTANCE
  • interferon-gamma receptor
  • irradiated cercariae
  • pulmonary responses
  • trypanosoma-brucei
  • cyto-toxicity
  • L-arginine
  • T-cell
  • mansoni
  • macrophages
  • resitance

Cite this

Nitric oxide produced in the lungs of mice immunized with the radiation-attenuate schistosome vaccine is not the major agent causing challenge parasite elimination . / Coulson, P S ; Smythies, L E ; Betts, C ; Mabbott, N A ; Sternberg, Jeremy M; Wei, X G ; Liew, F Y ; Wilson, R A .

In: Immunology, Vol. 93, No. 1, 01.1998, p. 55-63.

Research output: Contribution to journalArticle

Coulson, P S ; Smythies, L E ; Betts, C ; Mabbott, N A ; Sternberg, Jeremy M ; Wei, X G ; Liew, F Y ; Wilson, R A . / Nitric oxide produced in the lungs of mice immunized with the radiation-attenuate schistosome vaccine is not the major agent causing challenge parasite elimination . In: Immunology. 1998 ; Vol. 93, No. 1. pp. 55-63.
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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 defected 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.",
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T1 - Nitric oxide produced in the lungs of mice immunized with the radiation-attenuate schistosome vaccine is not the major agent causing challenge parasite elimination

AU - Coulson, P S

AU - Smythies, L E

AU - Betts, C

AU - Mabbott, N A

AU - Sternberg, Jeremy M

AU - Wei, X G

AU - Liew, F Y

AU - Wilson, R A

PY - 1998/1

Y1 - 1998/1

N2 - 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 defected 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.

AB - 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 defected 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.

KW - INTERFERON-GAMMA RECEPTOR

KW - IRRADIATED CERCARIAE

KW - PULMONARY RESPONSES

KW - TRYPANOSOMA-BRUCEI

KW - CYTO-TOXICITY

KW - L-ARGININE

KW - T-CELL

KW - MANSONI

KW - MACROPHAGES

KW - RESISTANCE

KW - interferon-gamma receptor

KW - irradiated cercariae

KW - pulmonary responses

KW - trypanosoma-brucei

KW - cyto-toxicity

KW - L-arginine

KW - T-cell

KW - mansoni

KW - macrophages

KW - resitance

U2 - 10.1046/j.1365-2567.1998.00405.x

DO - 10.1046/j.1365-2567.1998.00405.x

M3 - Article

VL - 93

SP - 55

EP - 63

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 1

ER -