1. Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration
- Author
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Neumann, B., Machleidt, T., Lifka, A., Pfeffer, K., Dietmar Vestweber, Mak, T. W., Holzmann, B., and Krönke, M.
- Subjects
Male ,Mice, Knockout ,Immunology ,Vascular Cell Adhesion Molecule-1 ,Intercellular Adhesion Molecule-1 ,Receptors, Tumor Necrosis Factor ,Immunoenzyme Techniques ,Mice, Inbred C57BL ,Mice ,Cell Adhesion ,Leukocytes ,Animals ,Immunology and Allergy ,Female ,Endothelium, Vascular ,E-Selectin ,Lung - Abstract
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.
- Published
- 1996