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 factor (PAF) and leukotriene B4 (LTB4) in vitro. The effect of the analogues N6-2'-O-dibut...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
1997-12-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800027 |
| _version_ | 1797713351758839808 |
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| author | Alessandra C Alves Ana Lucia A Pires Vincent Lagente Renato SB Cordeiro Marco A Martins Patricia MR e Silva |
| author_facet | Alessandra C Alves Ana Lucia A Pires Vincent Lagente Renato SB Cordeiro Marco A Martins Patricia MR e Silva |
| author_sort | Alessandra C Alves |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-6bdc6233980f4f89a2e630086e901a0f |
| institution | Directory Open Access Journal |
| issn | 0074-0276 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T07:35:07Z |
| publishDate | 1997-12-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-6bdc6233980f4f89a2e630086e901a0f2023-09-02T21:32:45ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80601997-12-019220120410.1590/S0074-02761997000800027Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitroAlessandra C AlvesAna Lucia A PiresVincent LagenteRenato SB CordeiroMarco A MartinsPatricia MR e SilvaIn 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800027eosinophilmigrationphosphodiesterase inhibitors |
| spellingShingle | Alessandra C Alves Ana Lucia A Pires Vincent Lagente Renato SB Cordeiro Marco A Martins Patricia MR e Silva Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro Memorias do Instituto Oswaldo Cruz eosinophil migration phosphodiesterase inhibitors |
| title | Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| title_full | Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| title_fullStr | Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| title_full_unstemmed | Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| title_short | Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| title_sort | effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro |
| topic | eosinophil migration phosphodiesterase inhibitors |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02761997000800027 |
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