Impact of MK-886 on H₂O₂ Generation by Human Neutrophils and Cell Degranulation

I. V. Gorudko¹ and A. V. Timoshenko^2*

¹Belarusian State University, pr. F. Skaryny 4, Minsk, 220050 Belarus; fax: (017) 220-7265; E-mail: gorudko@phys.bsu.unibel.by

²Institute of Photobiology, National Academy of Sciences of Belarus, ul. Akademicheskaya 27, Minsk, 220072 Belarus; E-mail: timoshenko@phys.bsu.unibel.by

^* To whom correspondence should be addressed.

Received February 1, 2000

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Metabolic inhibitors can clearly affect different aspects of the functional activity of cells. This property was studied in the present work with respect to MK-886, a well-known inhibitor of the 5´-lipoxygenase-activating protein. It was found that this inhibitor in a micromolar concentration range (2-20 µM) induced in a dose-dependent manner H₂O₂ generation by human neutrophils and the release of lysozyme from the cells. The MK-886-induced activation of neutrophils was accompanied by a significant decrease in N-(1-pyrene)maleimide-accessible SH-groups in the cells. According to its activity, MK-886 can be considered an agonist that causes up-regulation of inherent neutrophil functions. In summary, the results indicate that during the application of MK-886 as a 5´-lipoxygenase inhibitor in neutrophils, the impact of the compound on the functional activity of the cells should be taken into consideration.

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KEY WORDS: MK-886, neutrophil, lipoxygenase, hydrogen peroxide, degranulation, lysozyme

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