NITRIC-OXIDE PRODUCED IN THE LUNGS OF MICE IMMUNIZED WITH THE RADIATION-ATTENUATE SCHISTOSOME VACCINE IS NOT THE MAJOR AGENT CAUSING CHALLENGE PARASITE ELIMINATION

Mice vaccinated with radiation-attenuated cercariae of Schistosoma man soni exhibit high levels of protection against a challenge with normal larvae. The immune effector mechanism, which operates against schisto somula in the lungs, requires CD4(+) T cells capable of producing inte rferon-gamma (IFN-gamma). This cytokine can stimulate production of ni tric 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 as says on antigen-stimulated airway cell cultures. Enhanced levels of NO , compared with those in cultures from control mice, were defected bot h after vaccination and after challenge; elevated levels of iNOS mRNA were also present in whole lung after challenge. However, administrati on of an iNOS inhibitor to vaccinated mice after percutaneous challeng e did not significantly increase the worm burden. Furthermore, when mi ce with a disrupted iNOS gene were vaccinated they showed a highly sig nificant level of protection. Although NO from activated macrophages c an mediate cytotoxic killing of newly transformed schistosomula in vit ro, we have demonstrated that the addition of erythrocytes to these la rvicidal assays abolishes its effects. We interpret this to mean that once migrating schistosomula enter the bloodstream they will be protec ted against the cytotoxic actions of NO. Our data thus provide little evidence to implicate NO as a major component of the pulmonary effecto r response to S. mansoni in vaccinated mice.