EFFECT OF SELECTIVE PHOSPHODIESTERASE INHIBITORS ON THE RAT EOSINOPHIL CHEMOTACTIC RESPONSE IN-VITRO

In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE) type III, IV and V on eosinophil chemotaxis triggered by platelet activating facto r (PAF) and leukotriene B-4 (LTB4) in vitro. The effect of the analogu es N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt(2) cyclic AMP) and N2-2'-O-dibutyrylguanosine 3':5' cyclic monophosphate (Bt(2) cyclic GMP) has also been determined The eosinophils were obtained fr om the peritoneal cavity of naive Wistar rats and purified in disconti nuous Percoll gradients to 85-95% purity. We observed that pre-incubat ion of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association wit h an increase in the intracellular levels of cyclic AMP. In contrast n either zaprinast (type V inhibitor) nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt(2) cyclic AMP suppress the eo sinophil chemotaxis, under conditions where Btz cyclic GMP was ineffec tive. We have concluded that inhibition of PDE IV but not PDE III or V was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eos inophil accumulation may, at least, be partially dependent on their ab ility to directly inhibit the eosinophil migration.