1887

Abstract

Sporotrichosis, a mycosis caused by , is characterized by lymphocutaneous lesions. In immunocompromised hosts, this fungus may invade the bloodstream and disseminate to other tissues, such as lung and bone. Our group previously showed that yeasts adhere to endothelial monolayers and that this interaction is modulated by cytokines. Using 3.0 μm-pore culture inserts, the present work shows that transforming growth factor (TGF)-1 led to a 80±26 % increase in fungal migration across endothelial monolayers and inhibited fungus internalization by 55±23.5 %, when compared to untreated cells. The major surface endothelial molecules recognized by were not modulated by TGF-1. These data suggested that a paracellular route is preferentially used by during the transmigration of cultured endothelial cells. It was further observed that TGF-1 increased the subendothelial matrix exposure and that anti-fibronectin (anti-FN) and anti-laminin (anti-LM) antibodies abolished the increase in association with endothelial monolayers induced by TGF-1. These antibodies also inhibited (38.2±4.29 % and 50.8±17.3 %, respectively) the adhesion of to freshly prepared native endothelial matrices. Furthermore, transendothelial migration of was blocked by anti-FN and anti-LM antibodies. These data indicate that TGF-1-induced adhesion to endothelial monolayers results from the increased exposure of the subendothelial extracellular matrix and that this event may contribute to the enhancement of transendothelial migration.

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2007-09-01
2019-11-21
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