Roles of tumor necrosis factor p55 and p75 receptors in TNF-alpha-induced vascular permeability.
We have investigated the role of p55 and p75 tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2, respectively) in TNF-induced alteration of endothelial permeability in vitro and in vivo. Stimulation of TNFR1 with an agonist antibody or a receptor-selective TNF mutein increased the flux of (125)I-albumin through endothelial cell monolayers. An antagonist anti-TNFR1 antibody, but not antagonist anti-TNFR2 antibodies, blocked the activity of TNF in vitro. Stimulation of TNFR1, but not TNFR2, induced cytoskeletal reorganization associated with increased permeability. SB-203580, a p38 mitogen-activated protein kinase inhibitor, blocked TNFR1-induced cytoskeletal reorganization and permeability. A selective mouse TNFR1 agonist and human TNF, which binds to murine TNFR1, increased the leakage of trypan blue-albumin from liver vessels in mice. These results indicate that stimulation of TNFR1 is necessary and sufficient to increase endothelial permeability in vitro and in vivo. However, an antagonist anti-murine TNFR2 antibody partially inhibited the effect of murine TNF on liver vessels, suggesting that TNFR2 also plays a role in the regulation of TNF-induced vascular permeability in vivo.
Ferrero
E
E
Department of Pathology and Molecular Medicine, San Raffaele H Scientific Institute, Milan, Italy. ferrero.elisabette@hsr.it
Zocchi
M R
MR
Magni
E
E
Panzeri
M C
MC
Curnis
F
F
Rugarli
C
C
Ferrero
M E
ME
Corti
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D022502:Stress Fibers / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000906:Antibodies; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha