Improvement of Polymorphonuclear Leucocyte Oxidative and Bactericidal Functions in Chronic Granulomatous Disease with4-Amino-4'-4 Hyndroxylaminodiphenyl Sulphone

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Abstract
To restore oxidant-dependent capabilities to chronic granulomatous disease (CGD) polymorphonuclear leukocytes (PMN), a dapsone derivative, 4-amino-4''-hydroxylaminodiphenyl sulfone (DDS-NOH), known to generate H2O2, was studied. After incubation of CGD PMN with 0.2 and 1.0 mM DDS-NOH for 30 min, the rate of glucose-I-14C oxidation via hexose monophosphate (HMP) shunt increased 2- to 4-fold and that of iodination of ingested zymosan particles 1.5- to 2.7-fold. Both effects could be further enhanced by superoxide dismutase (SOD) but inhibited by catalase. In 3 patients, 0.2 mM DDS-NOH improved in vitro killing of Staphylococcus aureus. DDS-NOH 0.02 mM induced capping of concanavalin (Con) A receptor complexes suggesting inferference by the drug with microtubule-associated function. Optimal concentrations of DDS-NOH may be employed as an oxidant to improve metabolic and bactericidal functions of PMN from patients with CGD.