title: Altered expression of neutrophil peripheral benzodiazepine receptor in X-linked chronic granulomatous disease.
abstract: This study was aimed at determining whether the peripheral benzodiazepine receptor (PBZDR), which is abundantly expressed on mononuclear phagocytes, is involved in host defense mechanisms depending on phagocyte membrane-associated NADPH-oxidase complex. Analysis by reversible and covalent binding of PBZDR expression on human neutrophils shows that it is modulated during NADPH-oxidase activation with phorbol 12-myristate 13-acetate. Based on a series of 17 patients with chronic granulomatous disease (CGD), results show that PBZDR expression is dramatically impaired in X-linked CGD, an inherited disorder due to a mutation on the gene coding for cytochrome b558 NADPH-oxidase component, whereas it is unaffected in autosomal recessive CGD where cytochrome b558 is normally expressed, suggesting a link between PBZDR and cytochrome b558 expressions. PBZDR can be assigned by covalent binding to an 18-Kd membrane protein. These results suggest that the neutrophil PBZDR, which can accommodate the widely prescribed anxiolytic drug Valium (diazepam), is involved in host defense against pathogens, a function that could be affected by neuroimmune interactions.
authors.affiliation: INSERM U25, Hôpital Necker, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Zavala
authors.forename: F
authors.initials: F
authors.lastname: Veber
authors.forename: B
authors.initials: B
authors.lastname: Descamps-Latscha
mesh_terms: D004789:Enzyme Activation / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008040:Genetic Linkage; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism / Q000502:physiology; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014960:X Chromosome
chemical_list: D011963:Receptors, GABA-A; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases