title: 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.
abstract: Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up-regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction 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 125I-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell, which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selection 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 and in allergic diseases.
authors.affiliation: Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, South Australia.
authors.forename: E I
authors.initials: EI
authors.lastname: Korpelainen
authors.forename: J R
authors.initials: JR
authors.lastname: Gamble
authors.forename: W B
authors.initials: WB
authors.lastname: Smith
authors.forename: G J
authors.initials: GJ
authors.lastname: Goodall
authors.forename: S
authors.initials: S
authors.lastname: Qiyu
authors.forename: J M
authors.initials: JM
authors.lastname: Woodcock
authors.forename: M
authors.initials: M
authors.lastname: Dottore
authors.forename: M A
authors.initials: MA
authors.lastname: Vadas
authors.forename: A F
authors.initials: AF
authors.lastname: Lopez
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016185:Receptors, Interleukin-3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016209:Interleukin-8; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha