TY - JOUR
T1 - Role of eosinophil peroxidase in host defense and disease pathology
AU - Wang, Jianguo
AU - Slungaard, Arne
PY - 2006/1/15
Y1 - 2006/1/15
N2 - Three unusual substrates-bromide (Br-), nitrite (NO 2-), and thiocyanate (SCN-)-compete for oxidation by eosinophil peroxidase (EPO) in physiologic fluids in the presence of H2O2 to yield, respectively, hypobromous acid (HOBr), nitrogen dioxide (NO2.), or hypothiocyanous acid (HOSCN). These oxidant products have strikingly different reactivities: HOBr and NO 2. are potent, widely reactive, membrane-lytic oxidants whereas HOSCN is a weak, SH-specific oxidant that penetrates into cells and imposes an intracellular oxidant stress that can activate kinase pathways and transcription factors that profoundly influence gene expression in host cells. All three oxidants are lethal for pathogens. SCN- is the strongly preferred substrate for the EPO/H2O2. Specific biomarkers document that EPO-dependent oxidants are generated at sites of inflammation, but direct evidence that these oxidants cause disease is confined to the observation that an EPO knockout mouse line has dramatically less pathologic damage than do wild type animals in a murine model of ulcerative colitis.
AB - Three unusual substrates-bromide (Br-), nitrite (NO 2-), and thiocyanate (SCN-)-compete for oxidation by eosinophil peroxidase (EPO) in physiologic fluids in the presence of H2O2 to yield, respectively, hypobromous acid (HOBr), nitrogen dioxide (NO2.), or hypothiocyanous acid (HOSCN). These oxidant products have strikingly different reactivities: HOBr and NO 2. are potent, widely reactive, membrane-lytic oxidants whereas HOSCN is a weak, SH-specific oxidant that penetrates into cells and imposes an intracellular oxidant stress that can activate kinase pathways and transcription factors that profoundly influence gene expression in host cells. All three oxidants are lethal for pathogens. SCN- is the strongly preferred substrate for the EPO/H2O2. Specific biomarkers document that EPO-dependent oxidants are generated at sites of inflammation, but direct evidence that these oxidants cause disease is confined to the observation that an EPO knockout mouse line has dramatically less pathologic damage than do wild type animals in a murine model of ulcerative colitis.
KW - Allergy
KW - Bromide
KW - Eosinophil peroxidase
KW - Nitrite
KW - Parasite
KW - Thiocyanate
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U2 - 10.1016/j.abb.2005.10.008
DO - 10.1016/j.abb.2005.10.008
M3 - Article
C2 - 16297853
AN - SCOPUS:30544453606
SN - 0003-9861
VL - 445
SP - 256
EP - 260
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -