Pentoxifylline Inhibits Adhesion and Activation of Human T Lymphocytes

Abstract

We have herein studied the effect of pentoxifylline (PTX) on the adhesion and activation of human T lymphocytes. We found that PTX inhibited the adhesion of T cells to the beta1 and beta2 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 beta1 integrins induced by intracellular signals; however, the conformational change of beta1 integrins induced by extracellular stimuli (e.g., activating mAbs, or Mn2+) was not significantly affected by this drug. In addition, the homotypic aggregation of T cells induced by anti-beta1 and -beta2 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-2R alpha-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+ and the activation of the Na+/H+ 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.