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

Jpn J Pharmacol. 1995 Jul;68(3):353-7. doi: 10.1254/jjp.68.353.

Abstract

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.

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Indomethacin / pharmacology
  • Leukocytes / drug effects*
  • Leukotriene B4 / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Pyrroles / pharmacology*
  • Thiazoles / pharmacology*

Substances

  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Thiazoles
  • KB 3022
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Dexamethasone
  • Indomethacin