Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin- induced acute lung injury

A. Ishizaka, N. Hasegawa, F. Sakamaki, S. Tasaka, H. Nakamura, K. Kishikawa, A. Yamada, T. Obata, K. Sayama, T. Urano, M. Kanazawa

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19 Citations (Scopus)

Abstract

The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS + ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS + ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.

Original languageEnglish
Pages (from-to)1325-1331
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume150
Issue number5 I
DOIs
Publication statusPublished - 1994 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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