Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production.
The effects of pentoxifylline (Trental) on human neutrophil CR3 up-modulation, degranulation, and superoxide production were studied. We used the chemotactic peptide fMLP and the phorbol ester PMA as soluble stimuli, and beta-glucan particles as a CR3-specific solid phase stimulus of neutrophil superoxide production. Since neutrophils have adenosine A2 receptors, we compared effects of pentoxifylline to effects of adenosine, and we also looked at the effect of cytochalasin B, which breaks up actin filaments. Pentoxifylline inhibited both CR3 up-modulation and degranulation of myeloperoxidase and lysozyme. Pentoxifylline is a more potent inhibitor of fMLP- compared to PMA-induced degranulation, and is especially potent against superoxide production. While pentoxifylline is less potent than adenosine in its inhibition of fMLP-induced superoxide production, it is more potent in its inhibition of PMA- and beta-glucan particle-stimulated superoxide production. Cytochalasin B, which enhances degranulation and fMLP-stimulated superoxide production, was found to inhibit beta-glucan particle-stimulated superoxide production. These findings are consistent with the hypothesis that pentoxifylline can affect both the cytoskeletal architecture of unstimulated neutrophils and the activation and responses of neutrophils which involve actin polymerization and receptor-cytoskeletal interactions.
Currie
M S
MS
Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Durham, North Carolina 27705.
Rao
K M
KM
Padmanabhan
J
J
Jones
A
A
Crawford
J
J
Cohen
H J
HJ
D000241:Adenosine / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D003599:Cytoskeleton / Q000502:physiology; D005936:Glucans / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D011951:Receptors, Complement / Q000032:analysis*; D017463:Receptors, Complement 3b; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013805:Theobromine / Q000031:analogs & derivatives*
D005936:Glucans; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; D013805:Theobromine; D010431:Pentoxifylline