A novel thromboxane synthetase inhibitor, DP-1904, inhibits human blood eosinophil degranulation.
Eosinophils have been recognized to be associated with various immune responses and disease processes including bronchial asthma. Eosinophils release a number of cytotoxic and neurotoxic mediators. However, the factors regulating such release and the underlying mechanisms are unclear. In this study, we investigated the effect of a selective and potent thromboxane synthase inhibitor, DP-1904, on the release of eosinophil cationic protein (ECP) in platelet activating factor (PAF) and IgG-stimulated human blood eosinophils. PAF (1 microM) and IgG both released ECP which constituted about 25-30% of the total ECP content. The control protein, ovalbumin, did not release any ECP over the basal values. DP-1904 in two different concentrations, 10 microM and 100 microM, significantly attenuated the release of ECP in response to PAF or IgG. The mean percent inhibition by 10 microM DP-1904 was 49 +/- 10 and 31 +/- 2 against PAF and IgG-induced ECP release, respectively. However, at 100 microM DP-1904 the percent inhibition was 76 +/- 14 and 67 +/- 2, respectively. These data suggest that TXA2 is an important mediator in the regulation of eosinophil degranulation, and DP-1904 thus might prove beneficial in the treatment of bronchial asthma.
Agrawal
D K
DK
Creighton University School of Medicine, Omaha, Nebraska, USA.
Takami
M
M
Ono
S
S
D001249:Asthma / Q000097:blood; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002469:Cell Separation; D004341:Drug Evaluation; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D012260:Ribonucleases; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007093:Imidazoles; D013764:Tetrahydronaphthalenes; C056295:nafagrel; D012260:Ribonucleases; D013930:Thromboxane-A Synthase