Inhibition of eotaxin-mediated human eosinophil activation and migration by the selective cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram.
1. The effect of the selective type 4 phosphodiesterase (PDE 4) inhibitor rolipram on human eosinophil activation and migration mediated by eotaxin was investigated. 2. Studies were performed with human freshly isolated eosinophils from peripheral blood of healthy donors by a magnetic cell separation (MACS) technique to a purity > 99%. To test the effect of rolipram, eosinophils were stimulated with recombinant human eotaxin and the cell surface activation markers CD11b and L-selectin were analysed by flow cytometry. Furthermore, eotaxin mediated eosinophil migration was measured in a transendothelial chemotaxis assay. 3. Our results indicate that rolipram inhibited eotaxin-induced CD11b up-regulation up to 60.6 +/- 7.6% at the highest tested dose (10 microM), whereas transendothelial chemotaxis was partially inhibited reaching a plateau of approx. 30% at a rolipram concentration of 0.1 microM. 4. We conclude that the selective PDE 4 inhibitor rolipram decreases eotaxin mediated eosinophil activation, an observation that may contribute to elucidate the mechanism by which PDE 4 inhibitors reduce antigen-induced eosinophil infiltration in different animal models of allergic inflammation.
Santamaria
L F
LF
Grupo Farmacéutico Almirall, S. A. Research Center, Barcelona, Spain.
Palacios
J M
JM
Beleta
J
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram; D015854:Up-Regulation
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D011760:Pyrrolidinones; D019041:L-Selectin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020889:Rolipram