CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression.
Cultured human umbilical vein endothelial cells (EC) constitutively express a low level of CD40 antigen as detected by monoclonal antibody binding and fluorescence flow cytometric quantitation. The level of expression on EC is increased about 3-fold following 24 h treatment with optimal concentrations of tumor necrosis factor, interleukin 1, interferon beta, or interferon gamma; both interferons show greater than additive induction of CD40 when combined with tumor necrosis factor or interleukin 1. Expression of CD40 increases within 8 h of cytokine treatment and continues to increase through 72 h. A trimeric form of recombinant murine CD40 ligand acts on human EC to increase expression of leukocyte adhesion molecules, including E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. CD40 may be detected immunocytochemically on human microvascular EC in normal skin. We conclude that endothelial CD40 may play a role as a signaling receptor in the development of T-cell-mediated inflammatory reactions.
Karmann
K
K
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
Hughes
C C
CC
Schechner
J
J
Fanslow
W C
WC
Pober
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor