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Pentoxifylline inhibits adhesion and activation of human T lymphocytes
R González-Amaro1, D Portales-Pérez, L Baranda
1Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, México.
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.
Insights
Pentoxifylline (PTX) effectively inhibits human T lymphocyte adhesion and activation. This drug impacts cell signaling, proliferation, and expression of key activation markers, suggesting potential clinical relevance.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- T lymphocytes play a critical role in immune responses.
- Cell adhesion and activation are crucial for T cell function.
- Pentoxifylline (PTX) is a methylxanthine derivative with known anti-inflammatory properties.
Purpose of the Study:
- To investigate the effects of pentoxifylline (PTX) on human T lymphocyte adhesion and activation.
- To elucidate the specific mechanisms by which PTX influences T cell behavior.
Main Methods:
- Assessed T cell adhesion to ICAM-1 and VCAM-1.
- Evaluated integrin activation and conformational changes.
- Measured T cell homotypic aggregation.
- Quantified expression of activation antigens (CD25, CD69, CD45RO).
- Monitored intracellular calcium flux and Na+/H+ antiporter activity.
- Analyzed cell cycle progression and proliferation via CD3/TCR stimulation.
Main Results:
- PTX dose-dependently inhibited T cell adhesion to VCAM-1 and ICAM-1.
- PTX interfered with intracellular signal-induced beta1 integrin activation but not extracellular stimuli-induced changes.
- Homotypic T cell aggregation was inhibited by PTX.
- PTX reduced PHA-induced expression of CD25, CD69, and CD98.
- PTX impaired early activation events like intracellular Ca2+ rise and Na+/H+ antiporter activation.
- PTX inhibited CD3/TCR-induced T cell cycle progression and proliferation.
- PTX did not affect PMA plus ionomycin-induced activation/proliferation.
Conclusions:
- Pentoxifylline (PTX) demonstrates significant inhibitory effects on human T lymphocyte adhesion and activation.
- PTX interferes with multiple pathways critical for T cell immune responses.
- These findings suggest potential therapeutic applications for PTX in conditions involving T cell hyperactivity.