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Neutrophils autoinactivate secretory products by myeloperoxidase- catalyzed
oxidation
RA Clark and N Borregaard
The neutrophil response to inflammatory stimuli involves the formation of
reactive oxygen species and secretion of granule enzymes. In studying
secretion of vitamin B12 binding protein by human neutrophils, we noted a
major decrease in total recoverable activity from the extracellular fluid
plus the stimulated cells (54% of resting cells). Recovery of B12 binding
protein from neutrophils exposed to phorbol myristate acetate or opsonized
zymosan was significantly enhanced on addition of heme enzyme inhibitors
(azide, cyanide) or catalase or when halide-free medium was used. The
changes in B12 binding protein recovery were attributable entirely to
increases in extracellular fluid levels, and cell pellet content was
unaffected. These data indicate extracellular destruction of functional B12
binding protein by the halide-dependent heme enzyme myeloperoxidase and
H2O2. Kinetic studies demonstrated rapid secretion of B12 binding protein
in the first two to five minutes, followed by its inactivation over the
next 20 to 30 minutes. A cell-free extract of vitamin B12 binding protein
was readily inactivated on exposure to purified myeloperoxidase, H2O2, and
a halide. These findings document a functional interaction among products
of the neutrophil specific granules (B12 binding protein), azurophil
granules (myeloperoxidase), and metabolic burst (H2O2). They provide an
interesting model for the modulation of the inflammatory response by
oxidation of secretory products of neutrophils.
Volume 65,
Issue 2,
pp. 375-381,
02/01/1985
Copyright © 1985 by The American Society of Hematology
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