Tumour necrosis factor induction of ELAM-1 and ICAM-1 on human umbilical vein endothelial cells--analysis of tumour necrosis factor-receptor interactions.
Induction of the adhesion molecules ELAM-1 and ICAM-1 on endothelial cells is a key pro-inflammatory effect of tumour necrosis factor (TNF). Earlier work in non-human systems has suggested that unlike other cell types, endothelial cells interact with the N-terminus of the TNF molecule, thereby implying novel TNF receptors on endothelial cells. This is also supported by 125I-TNF cross-linking studies on bovine endothelial cells. The present study aimed to see whether TNF induction of ELAM-1 and ICAM-1 on human umbilical vein endothelial cells (HUVECs) involved novel TNF-receptor interactions. Three approaches were employed. First, antibodies directed at different sites on the TNF molecule were tested for inhibition of TNF-induction of ELAM-1 and ICAM-1 on HUVECs. Inhibition was seen only with antibodies reacting with epitopes outside the N-terminal region. Second, an N-terminal TNF peptide (residues 1-26) failed to induce ELAM-1 and ICAM-1 on HUVECs or antagonise TNF induction of these molecules. Third, HUVEC/125I-TNF cross-linking revealed a major complex characteristic of the known 55 kDa TNF receptor: this was confirmed with receptor-specific monoclonal antibodies. It is concluded that (a) the same part of the TNF molecule interacts with TNF-receptors on HUVECs and other cell types and (b) TNF induction of ELAM-1 and ICAM-1 on HUVECs is mediated via the well-characterized 55 kDa TNF receptor.
Thorp
K M
KM
Yamanouchi Research Institute, Littlemore Hospital, Oxford.
Southern
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C
Bird
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IN
Matthews
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D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003432:Cross-Linking Reagents; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007457:Iodine Radioisotopes; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D019040:E-Selectin; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C076419:tumor necrosis factor (1-26); D018799:Intercellular Adhesion Molecule-1