Restitution of superoxide generation in autosomal cytochrome-negative chronic granulomatous disease (A220 CGD)-derived B lymphocyte cell lines by transfection with p22Phox cDNA

Friedrich E. Maly, Cornelia C. Schuerer-Maly, Lawrence Quilliam, Charles G. Cochrane, Peter E. Newburger, John T. Curnutte, Mary Gifford, Mary C. Dinauer

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The respiratory burst oxidase of phagocytes and B lymphocytes is a multicomponent enzyme that catalyzes the one-electron reduction of oxygen by NADPH. It is responsible for the O2 production that occurs when these cells are exposed to phorbol 12-myristate 13-acetate or physiologic stimuli, such as phagocytosis in phagocytes or cross-linking of surface immunoglobulin in B lymphocytes. The activity of this enzyme is greatly diminished or absent in patients with chronic granulomatous disease (CGD), an inherited disorder characterized by a severe defect in host defense against bacteria and fungi. In every CGD patient studied so far, an abnormality has been found in a gene encoding one of the four components of the respiratory burst oxidase: the membrane proteins p22Phox or gp91Phox which together form the cytochrome b558 protein, or the cytosolic proteins p47Phox or p67Phox. Autosomal recessive cytochrome-negative CGD (A220 CGD) is associated with mutations in the gene coding for p22Phox. We report here that the capacity for O2 production and cytochrome b558 protein expression were restored to Epstein-Barr virus-transformed B lymphocytes from two A220 CGD patients by transfection with an expression plasmid containing a p22Phox cDNA. No detectable O2 was generated by untransfected p22Phox-deficient lymphocytes. The genetic reconstitution of the respiratory burst in A220 CGD B lymphocytes by transfer of the wild-type p22Phox cDNA represents a further step towards somatic gene therapy for this subgroup of A220 CGD. This system will also be useful for expression of genetically engineered mutant p22Phox proteins in intact cells, facilitating the structure-function analysis of cytochrome b558.

Original languageEnglish (US)
Pages (from-to)2047-2053
Number of pages7
JournalJournal of Experimental Medicine
Volume178
Issue number6
DOIs
StatePublished - Dec 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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