Inhibitory Activity of Pranlukast and Montelukas Against Histamine Release and LTC4 Production from Human Basophils
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概要
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Leukotriene receptor antagonists (LTRAs) are routinely used to treat bronchial asthma and are thought to act mostly by inhibiting leukotriene receptors. However, there is no preclinical or clinical evidence of the direct effect of LTRAs on histamine release from and leukotriene (LT) C4 production by basophils. We used anti-IgE antibody (Ab), FMLP, and C5a to induce histamine release, and anti-IgE Ab and FMLP to stimulate LTC4 production. Basophils were exposed to different concentrations of pranlukast and montelukast, and then to anti-IgE Ab, FMLP, and C5a. Culture supernatant histamine and LTC4 levels were measured by using a histamine ELISA kit and a LTC4 EIA kit, respectively. Histamine release was expressed as a percentage of the total histamine content (%HR) induced by anti-IgE Ab, FMLP, or C5a. To evaluate the effects of pranlukast and montelukast on histamine release and LTC4 production, we calculated the percent inhibition of histamine release and LTC4 production, expressed as percent inhibition, at different concentrations of pranlukast and montelukast. Pranlukast significantly inhibited histamine release stimulated by FMLP and C5a, but had no effect on histamine release stimulated by anti-IgE Ab. By comparison, montelukast significantly inhibited histamine release stimulated by FMLP, C5a, and anti-IgE Ab, in a concentration-dependent manner. Both pranlukast and montelukast significantly inhibited LTC4 production stimulated by anti-IgE Ab and FMLP. Together, these findings demonstrate that LTRAs have a direct inhibitory effect against histamine release and LTC4 production from basophils and provide new insight into the potential clinical application of LTRAs for the treatment of allergic disease.
- 昭和大学学士会の論文
昭和大学学士会 | 論文
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