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Effect Of Selective Phosphodiesterase Inhibitors On The Rat Eosinophil Chemotactic Response In Vitro
Alves, Alessandra C.; Pires, Ana Lucia A.; Lagente, Vincent; Cordeiro, Renato S.B.; Martins, Marco A. & E Silva, Patricia M.R.
Abstract
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 factor (PAF)
and leukotriene B4 (LTB4) in vitro. The effect of the analogues
N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP) and
N2-2' -O- dibutyrylguanosine 3' :5' cyclic monophosphate (Bt2 cyclic GMP) has
also been determined. The eosinophils were obtained from the peritoneal
cavity of naive Wistar rats and purified in discontinuous Percoll gradients
to 85-95% purity. We observed that pre-incubation of eosinophils with the
PDE type IV inhibitor rolipram suppressed the chemotactic response
triggered by PAF and LTB4, in association with an increase in the
intracellular levels of cyclic AMP. In contrast, neither 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 Bt2 cyclic AMP suppress the eosinophil chemotaxis, under
conditions where Bt2 cyclic GMP was ineffective. 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 eosinophil accumulation
may, at least, be partially dependent on their ability to directly inhibit
the eosinophil migration.
Keywords
eosinophil - migration - phosphodiesterase inhibitors
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