Evaluation of the effect of phosphodiesterase on equine platelet activation and the effect of antigen challenge on platelet phosphodiesterase activity in horses with recurrent airway obstruction.
OBJECTIVE
To determine whether expression of equine platelet activation-dependent surface markers is influenced by phospodiesterase (PDE) isoenzyme activity and whether antigen challenge alters platelet PDE activity in horses with recurrent airway obstruction (RAO).


METHODS
16 horses.


METHODS
7 healthy horses were used for in vitro experiments, 6 horses with RAO were used for antigen challenge, and 6 healthy horses were used as control animals. Three of the healthy horses had also been used in the in vitro experiments. Effects of PDE inhibition and activation of adenylyl cyclase on CD41/61 and CD62P expression on platelets and platelet-neutrophil aggregate formation in vitro were investigated via flow cytometry. Platelet PDE activity and sensitivity to inhibition of PDE3 and PDE5 isoenzymes were examined in horses with RAO and control horses before and after antigen challenge.


RESULTS
Inhibition of PDE or activation of adenylyl cyclase significantly inhibited stimulus-induced expression of CD41/61 and CD62P (by approx 94% and 40%, respectively) and percentage of CD62P positive cells (by approx 30%). Only the PDE3 inhibitor, trequinsin, caused a significant (53%) reduction in platelet-neutrophil aggregate formation. Platelet PDE activity decreased following antigen challenge in RAO-affected horses and control horses. In horses with RAO, a significant increase in sensitivity of platelet PDE to inhibition by the PDE5 inhibitor zaprinast was observed after 5 hours.


CONCLUSIONS
Results provided further evidence that PDE3 is an important regulator of equine platelet activation and suggested that changes in regulation of platelet PDE5 may contribute to antigen-induced response in horses with RAO.
Dunkel
Bettina
B
Department of Veterinary Clinical Sciences, The Royal Veterinary College, North Mymms, Herts AL9 7TA, England. bdunkel@rvc.ac.uk
Rickards
Karen J
KJ
Werling
Dirk
D
Page
Clive P
CP
Cunningham
Fiona M
FM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000402:Airway Obstruction / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002449:Cell Aggregation / Q000187:drug effects; D004789:Enzyme Activation; D006734:Horse Diseases / Q000097:blood* / Q000188:drug therapy; D006736:Horses; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000187:drug effects / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology*
D011688:Purinones; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; C011145:zaprinast