Role of reactive nitrogen species in neuronal cell damage during intestinal schistosomiasis

Free radicals are known to be involved in the host reaction during Schistos oma mansoni-induced inflammation in the liver and the intestine. In the pre sent study, the influence of reactive nitrogen species (RNS) on the enteric neurons of infected ileum of mice was investigated. Cryosections and whole -mounts of the ileum of control, and 8- and 15-week-infected mice were proc essed for immunohistochemical localization of 3-nitrotyrosine, a biomarker of RNS, and of active caspase-3, a key executioner of apoptosis. An antibod y directed against protein gene product 9.5 or S100 protein was used as a m arker for neurons or enteroglial cells. In infected mice, but not in contro l animals, 3-nitrotyrosine was detected in parasite eggs and, as revealed b y double immunolabelling, in some neuronal and enteroglial cells. Quantitat ive analysis of whole-mounts showed that the percentage of 3-nitrotyrosine- immunoreactive neurons significantly increased with time in both the submuc ous and myenteric plexus. Caspase-3 immunoreactivity was predominantly foun d in parasite eggs in infected mice. Immunoreactive enteric neurons were oc casionally observed. The results indicate that inflammation-induced RNS are present in the ileum of S, mansoni-infected mice, and participate in the e limination of the schistosome eggs causing damage in a significant number o f enteric neurons. However, neuronal cell death appears to be a rare phenom enon in the schistosome-infected mouse ileum.