Effects of CS-518, a thromboxane synthase inhibitor, on eosinophil function.
The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate) , a thromboxane A2 synthase inhibitor, on eosinophil accumulation and activation were investigated in an experimental asthmatic guinea pig model and several cellular models. In the in vivo studies, CS-518 inhibited the biphasic eosinophil accumulation in the bronchoalveolar lavage fluid, potently in the early phase, but less potently in the delayed phase. On the other hand, even at the lower dose, CS-518 completely inhibited the hypodensity of eosinophils in the delayed phase. In the in vitro studies, CS-518 suppressed thromboxane A2 production and potentiated prostaglandin I2 production from guinea pig eosinophils. Moreover, CS-518 and prostaglandin I2 suppressed chemotaxis, peroxidase release and superoxide generation in guinea pig eosinophils. In addition, the present studies provide further support for the possibility that thromboxane A2 and prostaglandin I2, which are produced in bronchoalveolar tissue and within eosinophils, are involved in modulation of eosinophil function and suggest that CS-518 is a potent inhibitor of eosinophil activation.
Itoh
K
K
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Mukaiyama
O
O
Satoh
Y
Y
Yamaguchi
T
T
Iizuka
Y
Y
D000818:Animals; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D010972:Platelet Activating Factor; D013876:Thiophenes; D013481:Superoxides; C055806:RS 5186; D013928:Thromboxane A2; D011464:Epoprostenol; D010544:Peroxidases; D013930:Thromboxane-A Synthase