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 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.
Korpelainen
E I
EI
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, South Australia.
Gamble
J R
JR
Smith
W B
WB
Goodall
G J
GJ
Qiyu
S
S
Woodcock
J M
JM
Dottore
M
M
Vadas
M A
MA
Lopez
A F
AF
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*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016209:Interleukin-8; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha