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The role of glutathione reductase in maintaining human granulocyte function
and sensitivity to exogenous H2O2
HJ Cohen, EH Tape, J Novak, ME Chovaniec, P Liegey and JC Whitin
Human granulocytes (polymorphonuclear leukocytes, PMN) produce H2O2 and
other reactive oxygen species while undergoing phagocytosis. To examine the
role of the glutathione cycle in metabolizing H2O2, we incubated PMN with
1,3-bis (2-chloroethyl) nitrosourea (BCNU). Incubation of PMN with BCNU
results in a dose-dependent inhibition of PMN glutathione reductase (GRED),
with 50% inhibition occurring at approximately 2 micrograms/mL BCNU. PMN
hexose monophosphate shunt activity stimulated with an exogenous
H2O2-generating system was inhibited only when the GRED activity was
reduced to less than 30% of control. BCNU-treated cells contained lower
levels of reduced sulfhydryls and reduced glutathione, which decreased even
more in the presence of an exogenous H2O2-generating system. The effect of
BCNU and exogenous H2O2 on various aspects of phagocytosis were examined.
Exposure of BCNU-treated PMN to an H2O2-generating system resulted in an
inhibition of chemotactic peptide-induced shape changes and degranulation.
The ability of BCNU-treated cells to produce O2- was diminished only when
the PMN were incubated with an H2O2-generating system in the presence of
cyanide. Ingestion of opsonized bacteria by BCNU-treated PMN was unaffected
by incubation in an H2O2-generating system even in the presence of cyanide.
We conclude that PMN GRED is inhibited by BCNU, the ability of PMN to
metabolize H2O2 is affected only when GRED is reduced more than 70%, this
inhibition affects the glutathione content of these cells, and some, but
not all of the phagocytic functions of GRED-inhibited PMN are inhibited
after exposure to an H2O2-generating system.
Volume 69,
Issue 2,
pp. 493-500,
02/01/1987
Copyright © 1987 by The American Society of Hematology
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