PENTOXIFYLLINE INHIBITS ADHESION AND ACTIVATION OF HUMAN T-LYMPHOCYTES

We have herein studied the effect of pentoxifylline (PTX) on the adhes ion and activation of human T lymphocytes, We found that PTX inhibited the adhesion of T cells to the P, and P, integrin ligands VCAM-1 and ICAM-1; this inhibitory activity was dose dependent, with a maximal ef fect from 12 to 24 h, We also found that PTX was able to interfere wit h the activation of P, integrins induced by intracellular signals; how ever, the conformational change of beta(1) integrins induced by extrac ellular stimuli (e,g,, activating mAbs, or Mn2+) was not significantly affected by this drug. In addition, the homotypic aggregation of T ce lls induced by anti-beta(1) and -beta(2) integrin chain mAbs was also inhibited by PTX, PTX had a significant inhibitory effect on the T lym phocyte expression of the activation Ags CD25 (IL-2R alpha-chain), CD6 9 (activation-inducer molecule), and CD98 (4F2) induced by PHA, Accord ingly, PTX also interfered with early cell activation events such as t he rise in intracellular Ca2+ and the activation of the Na+/H+ antipor ter 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 di d not show any effect on the cell activation/proliferation induced by PMA plus ionomycin, Our results indicate that PTX interferes efficient ly with the activation and cell adhesion of human T lymphocytes, These effects may be of relevance for the clinical uses of this drug.