Interferon-gamma induced nitric oxide mediates in vitro neuronal damage by Trypanosoma cruzi-infected macrophages.
Neuronal lesions and peripheral denervation in Chagas' disease are related to local inflammation; however, the pathogenic mechanisms of neuronal lesions in the heart and megavisceras are still unclear. We investigated the involvement of nitric oxide (NO) on neuronal lesion in co-cultures of neurons and macrophages. Trypanosoma cruzi-infected and interferon-gamma (IFN-gamma)-activated co-cultures of neurons and wild-type (WT) macrophages showed significant reduction of both neuronal survival and neurite density. These findings correlated with the levels of NO and the expression of inducible nitric oxide synthase (iNOS). Accordingly, neuronal survival rate in the co-cultures was recovered to control levels by treatment of the cultures with the iNOS inhibitor, aminoguanidine. Moreover, neither neuronal survival nor the neurite density was affected in the co-cultures when the macrophages were harvested from iNOS-deficient mice. These results demonstrate that iNOS-derived NO is the major molecule involved in neuronal damage mechanism in our in vitro model of Chagas' disease neuropathology.
Almeida-Leite
Camila Megale de
CM
Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Galvão
Lúcia Maria da Cunha
LM
Afonso
Luis C C
LC
Cunha
Fernando de Queiróz
FQ
Arantes
Rosa Maria Esteves
RM
D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000469:parasitology / Q000473:pathology*; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D014349:Trypanosoma cruzi
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine