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Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México; and
Departamento de Bioquímica, Facultad de Medicina, Universidad Complutense de Madrid, and
Sección de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain
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 ß1 and
ß2 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
ß1 integrins induced by intracellular signals; however,
the conformational change of ß1 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-ß1 and
-ß2 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
-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.
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