Pentoxifylline inhibits adhesion and activation of human T lymphocytes Article uri icon

abstract

  • We have herein studied the effect of pentoxifyline (PTX) on the adhesion and activation of human T lymphocytes. We found that PTX inhibited the adhesion of T cells to the t and 2 integrin ligands VCAM-1 and ICAM-1; this inhibitory activity was dose dependent, with a maximal effect from 12 to 24 h. We also found that PTX was able to interfere with the activation of β1 integrins induced by intracellular signals; however, the conformational change of β1 integrins induced by extracellular stimuli (e.g., activating mAbs, or Mn2%2b) was not significantly affected by this drug. In addition, the homotypic aggregation of T cells induced by anti-β1 and β2 integrin chain mAbs was also inhibited by PTX. PTX had a significant inhibitory effect on the T lymphocyte expression of the activation Ags CD25 (IL-2Rα-chain), CD69 (activation-inducer molecule), and CD98 (4F2) induced by PHA. Accordingly, PTX also interfered with early cell activation events such as the rise in intracellular Ca2%2b and the activation of the Na%2b/H%2b antiporter induced by PHA and phorbol esters, respectively. Furthermore, this drug inhibited both the cell cycle progression and cell proliferation of T cells induced through the CD3]TCR complex. However, this drug did not show any effect on the cell activation/proliferation induced by PMA plus ionomycin. Our results indicate that PTX interferes efficiently with the activation and cell adhesion of human T lymphocytes. These effects may be of relevance for the clinical uses of this drug.

publication date

  • 1998-01-01