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Effects of pentoxifylline on human polymorphonuclear neutrophil responses to TNF in whole blood
1INSERM U294, France.
Abstract:
We used flow cytometry to study the effects of pentoxifylline (PTX) on the expression of adhesion molecules and fMLP receptors on whole-blood polymorphonuclear neutrophils (PMN) in response to TNF, together with the oxidative burst and actin polymerisation. This technique analyses cells individually and avoids PMN activation related to isolation procedures. PTX reduced CD11b upregulation induced by TNF. Moreover, PTX reduced both TNF-induced binding of bacterial formyl peptides (fMLP) by human PMN and TNF priming of the PMN oxidative burst in response to these peptides. PTX also reduced TNF-induced actin polymerisation, which has been reported to participate in receptor cycling. This phenomenon could account in part for the ability of PTX to reduce fMLP binding to the PMN surface and subsequently to inhibit the PMN oxidative burst in response to fMLP. In addition to the PTX-induced decrease of TNF production, these effects on PMN could be beneficial in pathological conditions where high TNF production may induce excessive PMN activation, leading to vascular damage and tissue injury.
Insights
Pentoxifylline (PTX) reduces inflammatory responses in polymorphonuclear neutrophils (PMN). It inhibits tumor necrosis factor (TNF)-induced activation, adhesion molecule expression, and oxidative bursts, potentially mitigating vascular damage.
Area of Science:
- Immunology
- Pharmacology
Background:
- Tumor necrosis factor (TNF) is a key inflammatory cytokine.
- Polymorphonuclear neutrophils (PMN) play a critical role in inflammatory responses and vascular damage.
- Excessive PMN activation contributes to various pathological conditions.
Purpose of the Study:
- To investigate the effects of pentoxifylline (PTX) on PMN activation.
- To assess PTX's impact on adhesion molecules, fMLP receptors, oxidative burst, and actin polymerization in PMN.
- To evaluate PTX's potential therapeutic benefits in TNF-mediated inflammatory diseases.
Main Methods:
- Flow cytometry was used to analyze whole-blood PMN.
- Cells were studied individually to avoid isolation-induced activation.
- Effects of PTX on TNF-induced responses, including CD11b upregulation and fMLP binding, were measured.
Main Results:
- PTX significantly reduced TNF-induced CD11b upregulation on PMN.
- PTX inhibited TNF-induced binding of formyl peptides (fMLP) to PMN.
- PTX decreased TNF-primed PMN oxidative burst and TNF-induced actin polymerization.
Conclusions:
- Pentoxifylline modulates PMN function by reducing TNF-induced activation and adhesion.
- PTX's inhibition of fMLP binding and oxidative burst may be linked to reduced actin polymerization.
- These findings suggest PTX could be beneficial in conditions with high TNF production and excessive PMN activation, preventing vascular damage.