Inhibitory effect of KBT-3022, a new anti-platelet agent, on infiltration of polymorphonuclear leukocytes induced by leukotriene B4 or formyl-methionyl-leucyl-phenylalanine in mice.
We devised a method for evaluating polymorphonuclear leukocyte (PMN) infiltration in vivo employing an air bleb technique combined with measurement of myeloperoxidase (MPO) activity, and the effects of some anti-platelet agents were evaluated. KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and cilostazol inhibited the increase in MPO activity in the connective tissue around the air bleb induced by leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine (fMLP). Indomethacin inhibited only the fMLP-induced increase in MPO activity, but ticlopidine hydrochloride and acetylsalicylic acid had no effect. Histologic observation confirmed the inhibition of PMN infiltration by KBT-3022. These results indicate that KBT-3022 may be a potent inhibitor of both LTB4- and fMLP-induced infiltration of PMNs.
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D007975:Leukotriene B4 / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D013844:Thiazoles; C064847:KB 3022; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D007213:Indomethacin