Blood Journal
Leading the way in experimental and clinical research in hematology

Restoration of superoxide generation to a chronic granulomatous disease- derived B-cell line by retrovirus mediated gene transfer

  1. A Thrasher,
  2. M Chetty,
  3. C Casimir, and
  4. AW Segal
  1. Department of Medicine, Rayne Institute, University College London, UK.

Abstract

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.