Evidence for exclusive role in signalling of tumour necrosis factor p55 receptor and a potentiating function of p75 receptor on human endothelial cells.
The current study was undertaken to investigate the role of TNF-R75 in regulation of E-selectin and ICAM-1 expression by TNF on HUVEC. To this end, we used agonistic anti-TNF-R75 antibodies, being mAb MR2-1 and polyclonal antibodies anti-TNF-R75 (pAb75). The agonistic properties of these antibodies were ascertained by the costimulatory capacity in a T-cell proliferation assay. These anti-TNF-R75 antibodies bound effectively to HUVEC, as evidenced in binding studies using 125I-TNF, but they did not induce or enhance E-selectin or ICAM-1 expression as did agonistic anti-TNF-R55 antibodies. In contrast, both MR2-1 and pAb75 inhibited specifically TNF-induced E-selectin and ICAM-1 expression, but not activation by IL-1 or LPS. These results support the hypothesis, that in cells responding to TNF via the signalling pathway of the TNF-R55, the extracellular part of TNF-R75 captures TNF and delivers it to TNF-R55, resulting in an enhanced response to TNF.
Leeuwenberg
J F
JF
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
van Tits
L J
LJ
Jeunhomme
T M
TM
Buurman
W A
WA
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015703:Antigens, CD / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000166:cytology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019040:E-Selectin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D018799:Intercellular Adhesion Molecule-1