5-Lipoxygenase inhibitor (AA-861) attenuates neutrophil-mediated oxidative stress on the venular endothelium in endotoxemia

M. Suematsu, S. Miura, M. Suzuki, H. Nagata, T. Morishita, C. Oshio, M. Tsuchiya

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent microscope equipped with a Silicon Intensifier Target Image Tube camera and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes adhering to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E. coli, O-111 B4) was administered intravenously at a dose of 2 mg/kg/hour. After starting the infusion of endotoxin, the number of adherent cells gradually increased in the venular endothelium and was followed by a transient neutropenia. ChL activities from neutrophils were also significantly elevated, which may reflect the enhanced ability to generate oxygen-radicals. To elucidate the role of 5-lipoxygenase products in the locomotive and metabolic changes of neutrophils, the effects of AA-861, a specific inhibitor of 5-lipoxygenase was tested. In addition prednisolone and indomethacin were evaluated. AA-861 and prednisolone reduced neutropenia, leukocyte adhesion to the venular walls and ChL activities from neutrophils. It was concluded that 5-lipoxygenase may modulate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalJournal of Clinical and Laboratory Immunology
Volume25
Issue number1
Publication statusPublished - 1988 Jan 1

ASJC Scopus subject areas

  • Immunology

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