Efeitos do hormônio de crescimento sobre as células endoteliais tímicas

Abstract

Previous evidence shows that growth hormone (GH) modulates various intrathymic functions, including thymocyte migration induced by extracellular matrix (ECM) ligands and receptors. Cell migration is an essential event for intrathymic T-cell differentiation wich when finished their maturation in the thymus, enter the bloodstream and are addressed to secondary lymphoid organs. However, little is known about the influence of GH in the processes of entry and exit of cells in the thymus, which involve, among others, cell-cell and cell-ECM interactions. The aim of the present study was to evaluate the effects of GH on the thymic endothelial cells and its relation with the thymocytes. For the study, we used the murine thymic endothelioma cell line tEnd.1. Through assays of proliferation, it was verified that GH significantly increased the number of thymic endothelial cells treated for 8 or 24 hours in the concentration of 20 ng/mL. Furthermore, the cells treated with GH presented more vacuoles and more evident cytoplasmic ramifications. We examined by immunocytochemistry, the presence of ECM ligands in tEnd.1, showing na increase in the production of laminin and fibronectin, and by cytofluorometry, a reveled an increase in the expression of fibronectin receptors VLA-4 and VLA-5 in the tEnd.1 treated with GH. Accordingly, thymocyte adhesion to GH-treated tEnd.1 cells was increased, as compared to controls, and such an increase was seen regardless of the stage of thymocyte differentiation. Lastly, we showed that transendothelial migration of thymocytes in transwell chambers was lower when tEnd.1 cells were treated with GH and that this decline occurred mainly in CD4+CD8+ cells. In conclusion, the GH enhanced proliferation of endothelial cells and expression of ECM ligands and receptors by these cells. GH positively modulated adhesion tEnd.1/ thymocytes and negatively the transendothelial migration. These results support the notion that GH plays an important role in physiology of the thymus, comprising the key step of transendothelial thymocyte migration.