A novel thromboxane synthetase inhibitor, DP-1904, inhibits human blood eosinophil degranulation

Devendra K. Agrawal, Mitsutaka Takami, Shin Etsu Ono

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Abstract

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 μM) 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 μM and 100 μM, significantly attenuated the release of ECP in response to PAF or IgG. The mean percent inhibition by 10 μM DP-1904 was 49 ± 10 and 31 ± 2 against PAF and IgG-induced ECP release, respectively. However, at 100 μM 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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalInflammation
Volume21
Issue number1
DOIs
Publication statusPublished - 1997

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All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Immunology
  • Medicine(all)

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