We have reported that formyl peptide increases neutrophil-mediated eicosanoid production in the endoloxin-primed rat lung. To investigate the antiinflammatory role of a calcium antagonist (mibefradil), we injected mibefradil i.p. 18 hrs (30 mg/kg) and 2 hrs ( 15 mg/kg) before endotoxin (2 mg/kg, i.p.)-fMLP (250 μg/kg, i.v.) challenge in rats. We measured lung neutrophil accumulation using myeloperoxidase assay, and lung thromboxane 62 (TXB2) and leukotriene B4 (LTB4) production using enzyme immunoassay. Mibefradil suppressed neutrophil accumulation and eicosanoid production in lung tissue. To determine whether mibefradil affects the expression of adhesion molecules on endotoxin-primed neutrophils, we measured CD11b on human neutrophil incubated with endotoxin and mibefradil using flowcytometry. Endotoxin (10 ng/ml) increased CD11b expression on neutrophils, whereas mibefradil (10-6M) failed to suppress CD11b expression induced by endotoxin on neutrophils. We conclude that mibefradil suppressed lung neutrophil accumulation and neutrophil-mediated eicosanoid production in the lung, whereas the mechanism of the inhibitory effect of mibefradil on neutrophil sequestration into the lung is still unclear.
|Publication status||Published - 1996 Dec 1|
ASJC Scopus subject areas
- Molecular Biology