Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration.
Stimulation of leukocyte adhesion to the endothelium by TNF is mediated by the up-regulation of adhesion molecules on the endothelial cell surface. C57BL/6 mice and syngenic 55-kDa TNF receptor-deficient mice (TNFRp55-/- mice) were challenged with TNF, and the kinetics of intracellular adhesion molecule-1, ICAM-1, mucosal addressin cell adhesion molecule-1, vascular adhesion molecule-1 (VCAM-1), and E-selectin expression were examined in various organs. TNF induced sustained VCAM-1 expression within 4 h in lung, liver, and kidney. In the lungs, but not in other organs, transient E-selectin expression was induced by TNF within 0.5 h and peaked at 4 h. The TNF-induced expression of VCAM-1 and E-selectin was found to be exclusively controlled by the 55-kDa TNF-receptor (TNFRp55) as demonstrated by analysis of TNFRp55-/- mice. Furthermore, TNF triggered mononuclear cell and neutrophil infiltration of lung, liver, and kidney in C57BL/6 mice but not TNFRp55-/- mice. Interestingly, MAdCAM-1 expression in the marginal sinus of the spleen was detected in wild-type mice but was absent in TNFRp55-/- mice. Together, the data suggest that in vivo the 55-kDa TNF receptor mediates the induction of VCAM-1 and E-selectin expression and is critically involved in the control of leukocyte organ infiltration.
Neumann
B
B
Institute for Medical Microbiology and Hygiene, Technical University of Munich, Germany.
Machleidt
T
T
Lifka
A
A
Pfeffer
K
K
Vestweber
D
D
Mak
T W
TW
Holzmann
B
B
Krönke
M
M
D000818:Animals; D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019040:E-Selectin; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1