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Role of myeloperoxidase in the respiratory burst of human neutrophils
WM Nauseef, JA Metcalf and RK Root
Myeloperoxidase (MPO), a heme enzyme present in the primary granules of
polymorphonuclear leukocytes (PMNs), has been demonstrated to participate
in the oxygen-dependent microbicidal activity of these cells. Evidence for
the importance of MPO in this role comes in part from studies of normal
PMNs treated with the heme enzyme inhibitor, sodium azide. MPO has also
been suggested to regulate the respiratory activity of PMNs during
phagocytosis. The role of MPO in PMN oxygen metabolism was examined by
studying parameters of the respiratory burst of PMNs from a number of
unrelated MPO-deficient subjects; in addition, the ability of heme enzyme
inhibitors to duplicate the MPO-deficient state was studied by treating
normal and MPO-deficient cells with these compounds. MPO-deficient PMNs
were found to have a time-dependent hypermetabolic response as assessed by
measurement of oxygen consumption, superoxide generation, hydrogen peroxide
release, and hexose monophosphate shunt activity. Catabolic pathways for
hydrogen peroxide were normal, suggesting the increased recovery of oxygen
metabolites reflects increased production rather than decreased catabolism
of H2O2. These observations support the concept that MPO may play an
important role in terminating the respiratory burst of normal PMNs. The
three heme enzyme inhibitors studied--sodium azide, potassium cyanide, and
3-aminotriazole--differed greatly in the degree to which they inhibited
various enzymatic systems in the PMN. Nonetheless, as a group, they exerted
qualitatively similar effects on oxygen metabolism of normal and of
MPO-deficient PMNs. This indicates that many of the mechanisms by which
heme enzyme inhibitors influence PMN metabolism are independent of the
inhibition of MPO. Conclusions from studies using such treatment of PMNs
should be interpreted with caution.
Volume 61,
Issue 3,
pp. 483-492,
03/01/1983
Copyright © 1983 by The American Society of Hematology
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