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 respiration¹. Cytochrome b₋₂₄₅ is the only clearly defined component of this oxidase system and its absence² 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 burst³. Purification of the cytochrome has proved difficult, with uniform disagreement regarding the identity of its apoprotein, descriptions of its relative molecular mass (M_r) on SDS-polyacrylamide gel electrophoresis (PAGE) ranging from 10,000 to 127,000 (10–127K)^4–8. I report here that it has two subunits, a 23K protein and the previously described 76–92K glycoprotein⁹. 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.