Impaired granulocyte superoxide production and prolongation of the respiratory burst due to a low-affinity NADPH-dependent oxidase.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Shurin SB,Cohen HJ,Whitin JC,Newburger PE

subject

Has Abstract

pub_date

1983-09-01 00:00:00

pages

564-71

issue

3

eissn

0006-4971

issn

1528-0020

journal_volume

62

pub_type

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