The effect of pentoxifylline on human neutrophil migration: a possible role for cyclic nucleotides.

Relatively low concentrations of pentoxifylline caused a stimulation of random migration, while high concentrations inhibited chemotactic migration activated by formyl-methionyl-leucyl-phenylalanine (fMLP). The stimulating effect of pentoxyfylline was partly chemokinetic and partly chemotactic, and was dependent on extracellular calcium. Activation of migration by pentoxifylline was not dependent on the pore size of the micropore filter, indicating that the effect was not mediated by the ability of the drug to induce membrane deformability. Inhibitors of guanylate cyclase and antagonists of cGMP-dependent protein kinase (G-kinase) inhibited stimulation of migration by pentoxifylline. Pentoxyfylline caused a transient increase in cGMP level, while only high concentrations of pentoxifylline caused an increase in cyclic adenosine monophosphate (cAMP) level. It is suggested that the increase of migration is caused by cGMP and is mediated by a G-kinase, while the inhibition of migration at high concentrations of pentoxifylline is mediated by cAMP.