TY - JOUR
T1 - Binding of myeloperoxidase to bacteria
T2 - Effect on hydroxyl radical formation and susceptibility to oxidant-mediated killing
AU - Britigan, Bradley E.
AU - Ratcliffe, Heather R.
AU - Buettner, Garry R.
AU - Rosen, Gerald M.
N1 - Funding Information:
This work was supported in part by research grants from the VA Research Service and the Public Health Service (HL44275, AI28412, and AI34954). It was performed during the tenure of Dr. Britigan as an Established Investigator of the American Heart Association.
PY - 1996/8/13
Y1 - 1996/8/13
N2 - Neutrophils form superoxide anion (O2.-) and hydrogen peroxide (H2O2) and release myeloperoxidase (MPO) during ingestion of microbial pathogens, MPO, which adheres to some bacteria, catalyzes the formation of HOCl from H2O2, thereby enhancing H2O2/O2.- microbicidal activity, Hydroxyl radical (HO.), also is an important contributor to H2O2 and O2.- microbicidal activity. MPO decreases iron-catalyzed HO. production but also leads to HO. production through the reaction of O2.- and HOCl. We hypothesized that binding of MPO to bacteria could alter the magnitude and site of HO. production upon organism exposure to O2.-/H2O2. Incubation of MPO with Escherichia coli and Pseudomonas aeruginosa resulted in stable association of MPO with the bacteria which enhanced their susceptibility to killing by O2.-/H2O2. In the absence of MPO preincubation exposure of E. coli, but not P. aeruginosa to O2.-/H2O2, led to iron-catalyzed HO. generation. This was associated with different amounts of redox active iron in the two types of bacteria. MPO preincubation slightly decreased HO. detected with E. coli, but markedly increased HO. formation with P. aeruginosa. This likely resulted from decreased iron-catalyzed HO. production counterbalanced by increased iron-independent HO. formation. MPO preincubation did not effect bacterial killing by a system which generated only H2O2, precluding MPO-dependent HO. formation. These data are consistent with a possible role for MPO-derived HO. in the augmentation of bacterial killing by this enzyme.
AB - Neutrophils form superoxide anion (O2.-) and hydrogen peroxide (H2O2) and release myeloperoxidase (MPO) during ingestion of microbial pathogens, MPO, which adheres to some bacteria, catalyzes the formation of HOCl from H2O2, thereby enhancing H2O2/O2.- microbicidal activity, Hydroxyl radical (HO.), also is an important contributor to H2O2 and O2.- microbicidal activity. MPO decreases iron-catalyzed HO. production but also leads to HO. production through the reaction of O2.- and HOCl. We hypothesized that binding of MPO to bacteria could alter the magnitude and site of HO. production upon organism exposure to O2.-/H2O2. Incubation of MPO with Escherichia coli and Pseudomonas aeruginosa resulted in stable association of MPO with the bacteria which enhanced their susceptibility to killing by O2.-/H2O2. In the absence of MPO preincubation exposure of E. coli, but not P. aeruginosa to O2.-/H2O2, led to iron-catalyzed HO. generation. This was associated with different amounts of redox active iron in the two types of bacteria. MPO preincubation slightly decreased HO. detected with E. coli, but markedly increased HO. formation with P. aeruginosa. This likely resulted from decreased iron-catalyzed HO. production counterbalanced by increased iron-independent HO. formation. MPO preincubation did not effect bacterial killing by a system which generated only H2O2, precluding MPO-dependent HO. formation. These data are consistent with a possible role for MPO-derived HO. in the augmentation of bacterial killing by this enzyme.
KW - E. coli
KW - Hydroxyl radical
KW - Hypochlorous acid
KW - Myeloperoxidose
KW - P. aeruginosa
KW - Superoxide
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U2 - 10.1016/0304-4165(96)00014-1
DO - 10.1016/0304-4165(96)00014-1
M3 - Article
C2 - 8765125
AN - SCOPUS:0030582202
SN - 0304-4165
VL - 1290
SP - 231
EP - 240
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -