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- Title
Pentoxifylline Inhibits Tumor Necrosis Factor-α (TNFα)-Induced T-Lymphoma Cell Adhesion to Endothelioma Cells.
- Authors
Weiss, Johannes M.; Vanscheidt, Wolfgang; Pilarski, Kathrin A.; Weyl, Alice; Peschen, Manfred; Schöpf, Erwin; Vestweber, Dietmar; Simon, Jan C.
- Abstract
Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms, Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-α (TNFα), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNFα, but not of untreated endotheliotna cells, to bind T4ymphozna cells in dose-dependent (10-5-10-3 M) fashion. Selective incubation of either endothelioma cells or T- lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNFα stimulation. We questioned whether pentoxifylline suppressed T-lyznphoma edit endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNFα-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or α4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNFα-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.
- Subjects
PENTOXIFYLLINE; T cells; CELL adhesion; MOLECULES; ENDOTHELIOMA; NECROSIS
- Publication
Journal of Investigative Dermatology, 1995, Vol 104, Issue 5, p824
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12607010