Two forms of autosomal chronic granulomatous disease lack distinct neutrophil cytosol factors.
Chronic granulomatous diseases of childhood (CGD) are a group of disorders of phagocytic cell superoxide (O2.-) production (respiratory burst). Anion exchange chromatography separated from normal neutrophil cytosol a 47-kilodalton neutrophil cytosol factor, NCF-1, that restored activity to defective neutrophil cytosol from most patients with autosomally inherited CGD in a cell-free O2.--generating system. A 65-kilodalton factor, NCF-2, restored activity to defective neutrophil cytosol from one patient with autosomal CGD. NCF-1, NCF-2, and a third cytosol fraction, NCF-3, were inactive alone or in pairs, but together replaced unfractionated cytosol in cell-free O2.- generation. Neutrophils deficient in NCF-1, but not NCF-2, did not phosphorylate the 47-kilodalton protein. It is proposed that NCF-1, NCF-2, and NCF-3 are essential for generation of O2.- by phagocytic cells and that genetic abnormalities of these cytosol components can result in the CGD phenotype.
Nunoi
H
H
Bacterial Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Rotrosen
D
D
Gallin
J I
JI
Malech
H L
HL
D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D013481:Superoxides / Q000096:biosynthesis*
D010750:Phosphoproteins; D013481:Superoxides