Effects of pentoxifylline on human polymorphonuclear neutrophil responses to TNF in whole blood.
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.
Elbim
C
C
INSERM U294, France.
Lefebvre
M
M
Hakim
J
J
Gougerot-Pocidalo
M A
MA
D000199:Actins / Q000097:blood; D018845:CD11 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D019041:L-Selectin / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010431:Pentoxifylline / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018000:Receptors, Peptide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000199:Actins; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D010431:Pentoxifylline