Effects of endotoxin and verapamil on superoxide production by rat alveolar macrophage

Lee, Choon Taek; Kim, Keun Youl

doi:1993.40.3.223

Tuberc Respir Dis > Volume 40(3); 1993 > Article

Original Article

Tuberculosis and Respiratory Diseases 1993;40(3):223-235.
DOI: https://doi.org/10.4046/trd.1993.40.3.223 Published online June 1, 1993.

Effects of endotoxin and verapamil on superoxide production by rat alveolar macrophage

Choon Taek Lee¹, Keun Youl Kim²

¹Department of Intemal Medicine, Korea Cancer Center Hosþital, Seoul, Korea
²Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Abstract

Background
Superoxide anion which was produced by macrophage and neutrophil has a defensive role to kill invasive microorganisms and also an injurious role to produce self lung damage. Production of oxygen free radicals inciuding superoxide is a main mechanism of acute lung injury caused by bacterial endotoxin. Endotoxin is known to activate alveolar macrophage to produce increased oxygen free radicals after the stimulation with various biological materials (priming effect) Calcium is a very important intracellular messenger in that cellular process of superoxide production.
Methods
This experiment was performed to elucidate the effects of endotoxin and calcium on superoxide production by phorbol myristate acetate.stimulated alveolar macrophage and the effect of verapamil on priming effect of endotoxin.
Results
1) Preincubation of macrophages with endotoxin (E. coli 055-B5) primed the cells to respond with increased superoxide production after the stimulation with PMA. Priming with endotoxin (10^{-1>/sup>ug/ ml) produced a maximal enhancement of superoxide production (43%).
2) Verapamil could inhibit the superoxide production by PMA stimulated macrophage regardless of the presence of extracellular calcium. This means that the inhibitory effect of verapamil is caused by a mechanism independent of blocking calcium influx.
3) Verapamil could inhibit the priming effect of endotoxin on alveolar macrophage (from 30% increment to 13% increment) and could inhibit the superoxide productiòn by PMA.stimulated macrophage preincubated with endotoxin.

Conclusion
We concluded that verapamil could inhibit the superoxide production by PMA stimulated rat alveolar macrophage and also inhibit the priming effect of endotoxin on alveolar macrophage. These inhibitory effects of verapamil could be one of the mechanisms of verapamil effects on endotoxin induced lung injury.}

Key Words: Alveolar macrophage, Superoxide, End otoxin, Verapamil, Priming effect