Absence of both cytochrome b-245 subunits from neutrophils in X-linked chronic granulomatous disease

Abstract

Phagocytosis by neutrophils and other 'professional' phagocytic cells is accompanied by a microbicidal burst of non-mitochondrial respiration. Cytochrome b-245 is the only clearly defined component of this oxidase system and its absence provides the molecular basis of X-linked chronic granulomatous disease (CGD), in which a profound predisposition to infection results from complete failure of this respiratory burst. Purification of the cytochrome has proved difficult, with uniform disagreement regarding the identity of its apoprotein, descriptions of its relative molecular mass (Mr) on SDS-polyacrylamide gel electrophoresis (PAGE) ranging from 10,000 to 127,000 (10-127K). I report here that it has two subunits, a 23K protein and the previously described 76-92K glycoprotein. These subunits are closely linked and remain associated with the haem of the cytochrome through affinity and gel filtration chromatography and sucrose gradient centrifugation, and exhibit a similar distribution in a pH gradient. Neither protein was detected in the cells of five patients with X-linked CGD whereas both were present in two with the form of this disease with autosomal recessive inheritance.