title: Improvement of polymorphonuclear leucocyte oxidative and bactericidal functions in chronic granulomatous disease with 4-amino-4'-hydroxylaminodiphenyl sulphone.
abstract: In an effort to restore oxidant-dependent capabilities to chronic granulomatous disease (CGD) polymorphonuclear leucocytes (PMN), we studied a dapsone derivative, 4-amino-4'-hydroxylaminodiphenyl sulphone (DDS-NOH), known to generate H2O2. After incubation of CGD PMN with 0.2 and 1.0 mM DDS-NOH for 30 min, the rate of glucose-1-14C oxidation via hexose monophosphate (HMP) shunt increased 2--4-fold and that of iodination of ingested zymosan particles 1.5--2.7-fold. Both effects could be further enhanced by superoxide dismutase (SOD) but inhibited by catalase. In three patients, 0.2 mM DDS-NOH improved in vitro killing of Staph. aureus. DDS-NOH 0.02 mM induced capping of Concanavalin A (Con A) receptor complexes suggesting interference by the drug with microtubule-associated function. Thus, optimal concentrations of DDS-NOH may be employed as an oxidant to improve metabolic and bactericidal functions of PMN from patients with CGD.
mesh_terms: D000611:Aminobiphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D003208:Concanavalin A; D003622:Dapsone / Q000031:analogs & derivatives; D005947:Glucose / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007152:Immunologic Capping / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D000611:Aminobiphenyl Compounds; D003208:Concanavalin A; D003622:Dapsone; D002374:Catalase; D013482:Superoxide Dismutase; C018209:4-amino-4'-hydroxylaminodiphenylsulfone; D005947:Glucose