THE RECEPTOR FOR INTERLEUKIN-3 IS SELECTIVELY INDUCED IN HUMAN ENDOTHELIAL-CELLS BY TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES INTERLEUKIN-8 SECRETION AND NEUTROPHIL TRANSMIGRATION

Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is n ot normally found in bone marrow, raising doubts as to the in vivo rol e of IL-3. We have found that human umbilical vein endothelial cells ( HUVEC) express functional high-affinity receptors for IL-3 after stimu lation with tumor necrosis factor alpha (TNF-alpha), IL-1beta, or lipo polysaccharide, and that this receptor is involved in inflammatory phe nomena. TNF-alpha caused time- and dose-dependent upregulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occ urring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induc tion of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind I-125-labeled IL-3. Scatchard analysis under optima l conditions of TNF-alpha stimulation revealed almost-equal-to 1500 IL -3 receptors per cell, which were of a high-affinity class (K(d) = 500 pM) only. In contrast to a previous report, receptors for granulocyte -macrophage colony-stimulating factor could not be detected. IL-3 bind ing to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selectin expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation a nd in allergic diseases.