Expression and possible functional role of galectin-3 in the / Expressão e possível papel funcional da galectina-3 no timo de camundongos diabéticos não-obesos (NOD)

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Galectin-3 belongs to a family of endogenous lectins which bind to -galactosides presented on the cell surface and extracellular matrix glycoproteins. It is involved in multiple biological functions such as cell growth, adhesion, proliferation and apoptosis. Moreover, galectin-3 is found in several tissues and organs, being highly conserved among animal species. Recent papers related galectin-3 to autoimmune diseases such as insulin-dependent diabetes mellitus. This disease is characterized by pancreatic -cell destruction by T cells and auto-antibodies. NOD (non-obese diabetic) mice represent a suitable model to study diabetes, as they develop the disease in a similar way as humans. Previous data from our group showed important thymic alterations in these mice with the development of giant perivascular spaces, intermingled with an extracellular matrix network, suggesting a deficiency in the exit of mature thymocytes from the organ. This defect is associated with low expression of the fibronectin receptor VLA-5. Considering that galectin-3 is a de-adhesive protein recently related to the pathogenesis of type 1 diabetes, the aim of this study is to evaluate the participation of this lectin in the alterations observed in NOD thymus during the development of diabetes. In order to attend this objective, we evaluated galectin-3 expression in the thymus by immunohistochemistry; galectin-3 binding on thymocyte surface by flow cytometry, thymocyte migration in the presence of galectin-3 towards fibronectin in Transwell migration system; besides thymocyte exit from thymus under galectin-3 influence. We observed a significant increase in the number of galectin-3-positive cells in NOD thymus, mainly in the medulla. Moreover, we observed a significant increase of galectin-3 binding in the CD4-CD8- (double-negative) subset and a decrease in CD8 simple positive cells, when compared to BALB/c thymocytes. Interestingly, we verified that NOD thymocytes treated with galectin-3 migrate less than control thymocytes. These results led us to raise the hypothesis that galectin-3 migration under galectin-3 stimulus is VLA-5-dependent. Blocking assays with anti-VLA-5 antibody showed that thymocytes migrate less in the presence of the lectin when VLA-5 receptors were blocked, confirming our hypothesis. By the end, we observed that transendothelial migration of NOD thymocytes under galectin-3 influence is deficient, suggesting that this lectin plays an important role in the emigration of these cells to the periphery.

ASSUNTO(S)

inbred nod mice type 1 diabetes mellitus thymus gland galectina 3 imunologia celular camundongos endogâmicos nod diabetes mellitus tipo 1 galectin 3 timo

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