Caracterização das lesões periapicais induzidas em animais deficientes das enzimas iNOS e da subunidade GP91 da NADPH oxidase

Abstract

The development of periapical lesions is a consequence of host response against an endodontic infection. The nitric oxide synthase and the NADPH oxidase are responsible for generating reactive oxygen and nitrogen intermediates whose main action, amongst many others, is the resistance against pathogens. Phagocytes and other cellular types can produce these enzymes. The aim of this study was to investigate the immunologic and histological aspects of periapical lesion in C57BL/6 wild-type mice, iNOS-/- and PHOX-/-. The results showed that the iNOS-/- mice expressed high levels of IL-1, TNF-, RANK, RANKL and MCP-1 when compared to those with a deficiency in NADPH oxidase and to the wild-type one. The apical thickening of the periodontal ligament was greater in the iNOS-/- mice when compared with the other groups under study, indicating a greater bone resorption. A mild inflammatory infiltrate was noticed in the wild-type mice, as well as in the PHOX-/- ones, whereas the iNOS-/- mice had an intense mononuclear and polymorphonuclear infiltrate. We also evaluated the presence of T cells in the periapical lesion and in the adjacent bone marrow in three different post-operative stages: 3, 7, and 14 days after the induction of periapical lesion. There were T cells expressing mRANKL on day 3 and 7 after the operative procedures, but not on the 14th day. In turn, mRANKL+ T cells were found in the bone marrow in all pos-operative times. Fibroblasts and osteoblast expressing mRANKL were also detected 3 days after the periapical lesion induction. These findings suggest that the T cells, osteoblasts and the fibroblasts seem to be the cells responsible for the expression of mRANKL and, therefore, for the mediation of osteoclast differentiation in the earlier stages of the periapical lesion development. Furthermore, the microorganisms and their products present in the root canal infections of the C57BL/6 wild-type mice as well as in the PHOX-/- animals may interact with receptors of the innate immune response, inducing the expression of iNOS and the production of NO, which may control the infectious process in the periradicular tissues. The reactive oxygen intermediates seem not to play an important role in the resistance against bacterial infections in this model of study since the immunological and histological characteristics of the periapical lesion in PHOX-deficient animals are similar to those found in the C57BL/6 mice.