Interferon-y Upregulates Interleukin-3 (IL-3) Receptor Expression in Human Endothelial Cells and Synergizes With IL-3 in Stimulating Major Histocompatibility Complex Class I1 Expression and Cytokine Production

The human interleukin-3 (IL-3) receptor is constitutively expressed on certain hematopoietic cells where it mediates proliferation and differentiation, or functional activation. We have recently found that human umbilical vein endothelial cells (HUVECs) also express IL-3 receptors and that the expression is enhanced by stimulation with the monokine tumor necrosis factor a. In this report we show that the lymphokine interferon y (IFNy) is a powerful stimulator of the IL-3 receptor of HUVECs and that the combination of IL-3 and IFNy has a synergistic effect on major histocompatibility complex (MHCI class II expression and on the production of the early-acting hematopoietic cytokines IL-6 and granulocyte colony-stimulating factor (G-CSF). IFNy caused a timeand dose-dependent up-regulation of mRNA for both the LY and j3 chnins of the IL-3 receptor, with maximal effects occuring 12 to 24 hours after stimulation with IFNy at 100 U/ mL. Induction of mRNA correlated with protein expression on the cell surface, as judged by monoclonal antibody staining of both receptor chains and by the ability of HUVEC to specifically bind '251-labefed IL-3 ['a51-lL-3). Scatchard