Evaluation of the role of connexin 43 in the development of granuloma, experimentally induced in mice

Author(s)

Silvia Catarina Salgado Oloris

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2005-07-22

Examining board members

Maria Lucia Zaidan Dagli; Olga Célia Martinez Ibañez; Paulo César Maiorka; Mario Mariano; Sonia Jancar Negro

• Advisor: Maria Lucia Zaidan Dagli

Abstract

Inflammatory granulomatous disease involves coordinated interactions among lymphocytes, monocytes/macrophages, epithelioid cells, eosinophils, neutrophils and fibroblasts. Intercellular communication mediated by gap junctions constituted of connexins, is responsible for tissue homeostasis. Cx43 is present in lymphoid cells, myelogenous cells, fibroblasts and others. In order to understand the possible involvement of connexins in granuloma, we analyzed the effect of the heterologous deletion of a Gja1 (Cx43 gene) on the formation and development of hepatic granulomas induced by Schistosoma mansoni eggs. Heterozigous (Cx43+/-) and wild-type (Cx43+/+) mice were infected with S. mansoni cercarie and evaluated after 6, 8 and 12 weeks. Granuloma cells express Cx43, with considerable reduction in Cx43+/- mice. Moreover, granuloma cells from Cx43v+/- mice displayed reduced proliferation and increased collagen deposition at late phases of the disease. Despite these findings, no reduction of size or cellularity of the lesions was found in comparison to wild-type mice. We didn?t find differences in relation to blood count and splenic lymphocyte population CD4, CD8 and CD19. Peritoneal cells from animals of both genotypes presented similar production of NO and H2O2. However, blood neutrophils and monocytes from Cx43+/- mice, stimulated by PMA, displayed significantly increased oxidative burst. In conclusion, our results indicate that the deletion of one allele of the Cx43 gene clearly modifies the evolution of a granulomatous disease, supporting a role for this connexin on granuloma development. (AU)