Artrite experimental induzida por zymosan: caracterização citológica, histopatologica e imuno-histoquímica da sinovia e estudos histoquímico e bioquímico dos glicoconjugados da matriz condróide
Data
2000
Autores
Ramos, Ana Maria de Oliveira 
Orientadores
Patricio, Francy Reis da Silva
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A artrite cronica induzida por injecao intra-articular de Zy, em ratos Wistar, caracteriza-se, na fase aguda, por exsudacao de PMNs no liquido articular e na membrana sinovial, associada a erosao da sinovia, depositos de material fibrinoide e hiperplasia de sinoviocitos de revestimento, com presenca de linfocitos B, sugerindo participacao transitoria de linfocitos T CD4+ Th2. Os sinoviocitos mostram imuno-ativacao, as 72 horas, com gradativa substituicao dos PMNs por linfocitos e macrofagos, alem de inducao de significativa proliferacao vascular, com posterior formacao do pannus (l4 dias). Linfocitos expressando IL-2 podem ser vistos, desde o 71 dia, o que implica na participacao de celulas T CD4+ Th1, no processo. Linfocitos T CD8 , situados em torno de aglomerados de macrofagos, sao tambem observados e ha formacao de granulomas epitelioides, nao necroticos, com presenca de celulas gigantes tipo Langhans e progressiva deposicao de fibras colagenas. Concomitante, ha agressao a cartilagem articular, com formacao de fendas intersticiais e fragmentacao estrutural, degradacao do AH e reducao do conteudo de CS. AZy e, portanto, um modelo decorrente de resposta imunologica celular dependente de linfocitos T CD4+ Th1, com algumas alteracoes citologicas, histologicas, imunologicas e bioquimicas que se assemelham a AR e cujos parametros foram cronologicamente caracterizados. Este modelo podera ser ampliado e melhor dissecado visando o estudo do dano tissular mediado imunologicamente e ser usado para analise da atividade de linfocitos T Thl/Th2. Tambem permite dissecar algumas fases da reacao inflamatoria intra-articular cronica e se presta para testes de efeitos profilaticos de drogas, uma vez que se pode determinar, precisamente, o seu inicio e monitorizar sua evolucao. Pode ainda ser usado em investigacoes futuras sobre o papel da angiogenese no processo inflamatorio e na formacao do pannus
The zymosan-induced arthritis in Wistar rats evolves with polymorfonudear cell influx in the synovial fluid and membrane, associated with temporary hyperplasia of the synovial cells, which are immunologically activated at 72 hours. Presence of B cells can be demonstrated and seems to be associated with erosion and fibrin deposition on the synovium membrane, suggesting a transitory effect of T CD4+ Th2 lymphocytes. Proliferation of vessels can be seen at the ph day (p< 0,05) and the formation of the pannus occurs around the 14th day. Lymphocytes predominates during all the next stages of the lesion, with macrophage influx associated with presence of epithelioid granulomas and Langhans giant cells, surrounded by lymphocytes T CD8+. It is observed the expression of IL-2 by lymphocytes cells, suggesting the modulation by T lymphocytes CD4+ Th1 in the process. Fibrosis can be detected with collagen fiber deposition around the granulomas. Progressive degradation of the hyaluronic acid and reduction of the content of condroitin-sulphate of the cartilage is observed with the chronicity of the process. Zymosan-induced arthritis is, therefore, an experimental model of chronic arthritis caused by a transitory participation of Th2 cells, and mediated by an immunological response depending on the participation of T CD4+ Th1 cells and release of IL-2, with some cytological, histological, immunological and biochemical aspects that could be applied to the study of rheumatoid arthritis. It is an experimental model that could be used to assess treatments and the impact on Th1Th2 cells activity. The model allows studying the inflammatory reaction and it may be useful to test prophylactic and therapeutic effects of some drugs. It could also be broadened and be used for the study of angiogenesis during the inflammatory process and the evolution of the pannus.
The zymosan-induced arthritis in Wistar rats evolves with polymorfonudear cell influx in the synovial fluid and membrane, associated with temporary hyperplasia of the synovial cells, which are immunologically activated at 72 hours. Presence of B cells can be demonstrated and seems to be associated with erosion and fibrin deposition on the synovium membrane, suggesting a transitory effect of T CD4+ Th2 lymphocytes. Proliferation of vessels can be seen at the ph day (p< 0,05) and the formation of the pannus occurs around the 14th day. Lymphocytes predominates during all the next stages of the lesion, with macrophage influx associated with presence of epithelioid granulomas and Langhans giant cells, surrounded by lymphocytes T CD8+. It is observed the expression of IL-2 by lymphocytes cells, suggesting the modulation by T lymphocytes CD4+ Th1 in the process. Fibrosis can be detected with collagen fiber deposition around the granulomas. Progressive degradation of the hyaluronic acid and reduction of the content of condroitin-sulphate of the cartilage is observed with the chronicity of the process. Zymosan-induced arthritis is, therefore, an experimental model of chronic arthritis caused by a transitory participation of Th2 cells, and mediated by an immunological response depending on the participation of T CD4+ Th1 cells and release of IL-2, with some cytological, histological, immunological and biochemical aspects that could be applied to the study of rheumatoid arthritis. It is an experimental model that could be used to assess treatments and the impact on Th1Th2 cells activity. The model allows studying the inflammatory reaction and it may be useful to test prophylactic and therapeutic effects of some drugs. It could also be broadened and be used for the study of angiogenesis during the inflammatory process and the evolution of the pannus.
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Citação
RAMOS. Ana Maria de Oliveira. Artrite experimental induzida por zymosan: caracterização citológica, histopatologica e imuno-histoquímica da sinovia e estudos histoquímico e bioquímico dos glicoconjugados da matriz condróide. Tese (Doutorado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2000.