Restoration of superoxide generation to a chronic granulomatous disease-derived B-cell line by retrovirus mediated gene transfer.
Failure of a superoxide generating system, the NADPH oxidase, present in neutrophils and other phagocytes gives rise to chronic granulomatous disease (CGD), a group of single-gene inherited disorders all characterized by an extreme susceptibility to pyogenic infection, with potentially fatal consequences. About 30% of CGD cases are caused by an autosomally inherited deficiency of a 47-Kd cytoplasmic component of the oxidase (p47-phox). Epstein-Barr virus (EBV) immortalized B-lymphocyte lines established from these CGD patients also express this NADPH oxidase defect and consequently are rendered incapable of generating superoxide on stimulation. We have used a p47-phox-deficient EBV-transformed B-cell line as a recipient for retroviral transfer of a functional p47-phox cDNA. The presence and activity of the retrovirally encoded p47-phox in the transduced cells is demonstrated and we show that this restores their capacity to generate superoxide.
Thrasher
A
A
Department of Medicine, Rayne Institute, University College London, UK.
Chetty
M
M
Casimir
C
C
Segal
A W
AW
D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D015316:Genetic Therapy; D006105:Granulomatous Disease, Chronic / Q000378:metabolism / Q000628:therapy*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D019255:NADPH Oxidases; D013481:Superoxides / Q000378:metabolism*; D014162:Transfection
D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases