Five tumor necrosis factor-inducible cell adhesion mechanisms on the surface of mouse endothelioma cells mediate the binding of leukocytes.
We have distinguished five TNF-alpha-inducible cell adhesion mechanisms on microvasculature-derived endothelioma cells of the mouse which mediate the binding of different types of leukocytes. Three of these mechanisms could be identified as the mouse homologs of ICAM-1, VCAM-1, and E-selectin, of which the latter was defined by the novel mAb 21KC10. The fourth TNF-alpha-inducible cell adhesion mechanism was blocked by antibodies specific for mouse P-selectin. We have recently shown that TNF-alpha stimulates the synthesis of P-selectin in mouse endothelioma cells (A. Weller, S. Isenmann, D. Vestweber. 1992. J. Biol. Chem. 267:15176-15183). Here we show that this stimulation leads to maximal cell surface expression levels within 4 h after stimulation while the same endothelioma cells are also able to upregulate P-selectin at the cell surface within minutes after stimulation with PMA. Both effects are additive. The fifth TNF-induced cell adhesion mechanism is defined by mediating the binding to the mouse monocyte/macrophage cell line J774. This adhesion mechanism is not inhibited by antibodies against any of the other four CAMs; it functions well at 7 degrees C (in contrast to ICAM-1 and VCAM-1) and it is as active after 16 h of TNF induction as after 4 h (in contrast to E- and P-selectin). Furthermore, this new adhesion mechanism only functions on two of three endothelioma cell lines and is undetectable on the third, although ICAM-1, VCAM-1, E-selectin, and P-selectin could be demonstrated to function well on this cell line. Thus, in addition to the three known TNF-inducible CAMs, ICAM-1, VCAM-1, and E-selectin, also P-selectin and a fifth, as yet molecularly undefined cell adhesion mechanism, are TNF inducible at the cell surface of mouse endothelioma cells.
Hahne
M
M
Hans Spemann Laboratory, Max-Planck-Institute for Immunology, Freiburg, Germany.
Jäger
U
U
Isenmann
S
S
Hallmann
R
R
Vestweber
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D019040:E-Selectin; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D009000:Monocytes; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1