Increased respiratory burst in myeloperoxidase-deficient monocytes
RM Locksley, CB Wilson and SJ Klebanoff
Studies of the respiratory burst in myeloperoxidase (MPO) deficient
monocytes were undertaken to assess the physiologic consequence of the
absence of MPO in these cells. As previously demonstrated with neutrophils,
MPO-deficient monocytes had a greater initial rate, duration, and total
superoxide production in response to phagocytosis of zymosan than did
normal monocytes. Introduction of purified eosinophil peroxidase (EPO) into
the phagosome by binding the enzyme to the surface of the zymosan particles
changed the hypermetabolic characteristics of superoxide production in
MPO-deficient cells to more closely resemble normal cells, but had no
effect on superoxide generation by the normal monocytes. Further,
inactivation of the bound EPO before ingestion restored the supranormal
respiratory burst by the MPO-deficient cells. Iodination by MPO-deficient
monocytes was significantly depressed as compared to normal monocytes
following the ingestion of zymosan (1.9 versus 10.1 nmole I-/10(7)
monocytes/30 min; p less than 0.01). In contrast, iodination was markedly
augmented in MPO-deficient cells compared to normal cells after ingestion
of zymosan coated with EPO (208 versus 70 nmole I-/10(7) monocytes/30 min;
p less than 0.005), presumably reflecting the greater amounts of hydrogen
peroxide formed by MPO-deficient cells. There were no differences in the
levels of endogenous scavengers of reactive oxygen products (catalase,
superoxide dismutase, glutathione peroxidase and reductase, and total
glutathione) in MPO-deficient and normal monocytes that would account for
the enhanced respiratory burst of MPO-deficient cells. These findings
support a role for peroxidase in the termination of the respiratory burst
of monocytes.
Volume 62,
Issue 4,
pp. 902-909,
10/01/1983
Copyright © 1983 by The American Society of Hematology
