Studies of skin-window exudate human neutrophils: increased resistance to pentoxifylline of the respiratory burst in primed cells.
Human neutrophils were isolated both from peripheral blood (PB) and from aseptic inflammatory exudates obtained by the Senn's skin window technique (SW). The respiratory burst (O2- production) induced by in response to n-formyl-methionyl-lencyl-phenylalanine (fMLP) and by serum-treated zymosan (STZ) was investigated using a microplate assay. SW neutrophils were primed to enhanced fMLP-dependent O2- production in response to fMLP but not to STZ. Pentoxifylline, a cAMP-elevating drug, dose-dependently inhibited the respiratory burst in any experimental condition, but the dose-effect curves were markedly different according the stimulant used and the source of the cells. With fMLP as stimulant, a significant inhibition of the O2- production by PB neutrophils was obtained using doses of 10 micrograms/ml, while SW neutrophils were inhibited only by doses equal or higher than 100 micrograms/ml. With STZ as stimulant, the inhibition of the respiratory burst of PB neutrophils and of SW neutrophils was obtained only with doses higher than 400 micrograms/ml and 1 mg/ml respectively. Pentoxifylline dose-dependently (10 micrograms/ml to 1 mg/ml) increased the intracellular adenosine 3'-5'-cyclic monophosphate (cAMP) to the same extent in SW and in PB neutrophils. These data indicate that the priming of neutrophil oxidative metabolism by in vivo inflammation is associated with an increase in the resistance to the regulating effect of cAMP on the fMLP-dependent activation pathway of NADPH oxidase. The fact that therapeutic doses of pentoxifylline do not inhibit the respiratory burst of primed neutrophils may have relevance in the interpretation of the clinical effects of this drug.
Carletto
A
A
Institute of Medical Pathology, University of Verona, Italy.
Biasi
D
D
Bambara
L M
LM
Caramaschi
P
P
Bonazzi
M L
ML
Lussignoli
S
S
Andrioli
G
G
Bellavite
P
P
D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects; D012884:Skin Window Technique; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D000242:Cyclic AMP; D010431:Pentoxifylline