Transforming Growth Factor-β Regulates the Adhesive Interactions Between Mononuclear Cells and Microvascular Endothelium

Adhesion of leukocytes to the vascular endothelium is essential for the movements of cells from the bloodstream into inflammatory sites. In the present study, dermal microvascular endothelial cells (DMEC) isolated from normal porcine skin retained the capacity to adhere 51Cr-labeled porcine peripheral blood mononuclear cells (PBMC), nylon-wool — purified T cells, and isolated monocytes. Transforming growth factor-beta 1 (TGF-β) decreased the capacities of DMEC to support the adhesion of these cells in a dose-dependent manner. Maximal inhibition was observed with a TGF-β dose of 0.25 ng/ml and an incubation time of 6–12h. TGF-β did not affect the morphology of DMEC and had no adverse effect on the viability of the treated cells. The blocking effects of TGF-β on PBMC adhesion to DMEC was neutralized by a polyclonal turkey anti — TGF-β antiserum but not by control turkey serum. Although pretreatment of PBMC with TGF-β decreased the capacity of these cells to adhere to normal DMEC monolayers, kinetic studies demonstrated that these effects required between 4 and 8h incubation time. In addition, preincubation of DMEC with TGF-β completely blocked their response to the stimulating effects of TNF-α, IL-1-β, or both cytokines. Furthermore, TGF-β also abrogated the enhanced adhesiveness of DMEC pre-treated with TNF-α and IL-1-β. These findings suggest that TGF-β may play an important role in the down-regulation of inflammatory responses by decreasing vascular endothelial adhesiveness for mononuclear cells and monocytes