2Institute of Medical Physics and Biophysics, University of Leipzig, Liebigstrasse 27, Leipzig 04103, Germany; fax: (49-341) 971-5709; E-mail: email@example.com
3Russian State Medical University, ul. Ostrovityanova 1, 117513 Moscow, Russia; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received June 23, 2004; Revision received August 7, 2004
It was shown with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone that myeloperoxidase (MPO) in the presence of its substrates H2O2 and Cl- as well as activated neutrophils destroy tert-butyl hydroperoxide producing two adducts of O-centered radicals which were identified as peroxyl and alcoxyl radicals. Inhibitory analysis performed with traps of hypochlorite (taurine and methionine), free radical scavengers (2,6-di-tret-butyl-4-methylphenol and mannitol), and MPO inhibitors (salicylhydroxamic acid and 4-aminobenzoic acid hydrazide) revealed that the destruction of the hydroperoxide group in the presence of isolated MPO or activated neutrophils was directly caused by the activity of MPO: some radical intermediates appeared as a result of the chlorination cycle of MPO at the stage of hypochlorite generation, whereas the other radicals were produced independently of hypochlorite, presumably with involvement of the peroxidase cycle of MPO. The data suggest that the activated neutrophils located in the inflammatory foci and secreting MPO into the extracellular space can convert hydroperoxides into free radicals initiating lipid peroxidation and other free radical reactions and, thus, promoting destruction of protein-lipid complexes (biological membranes, blood lipoproteins, etc.).
KEY WORDS: myeloperoxidase, neutrophils, hypochlorite, tret-butyl hydroperoxide, free radicals, peroxyl radical, spin traps