Impaired granulocyte superoxide production and prolongation of the
respiratory burst due to a low-affinity NADPH-dependent oxidase
SB Shurin, HJ Cohen, JC Whitin and PE Newburger
A 7-yr-old girl with self-limited pulmonary aspergillosis was found to have
a defect in granulocyte superoxide production. Her cells produced
superoxide at 3% of control rates in response to phorbol myristate acetate
(PMA) and opsonized zymosan. Lag times for O-2 production were normal with
PMA, opsonized zymosan, and concanavalin-A stimulation. Her granulocyte
membranes depolarized in response to all of these stimuli. Superoxide
produced by podosomes and a particulate fraction demonstrated an enzyme
activity with a normal maximal velocity but a decreased affinity for NADPH.
NADH-dependent superoxide production by particles was similar with patient
and control material. The duration of superoxide production was prolonged
in the patient's intact granulocytes and in the particulate fractions from
her cells. Bacterial killing by the patient's granulocytes was initially
low, but approached control values after 90 min of incubation. These
results are explained by an enzyme activity that has a decreased affinity
for its substrate and a decreased rate of inactivation. Family studies
indicate an autosomal recessive mode of inheritance.
Volume 62,
Issue 3,
pp. 564-571,
09/01/1983
Copyright © 1983 by The American Society of Hematology
