Macrophage NADPH Oxidase Flavocytochrome b Localizes to the Plasma Membrane and Rab11-Positive Recycling Endosomes

被引:62
作者
Casbon, Amy-Jo [1 ]
Allen, Lee-Ann H. [4 ,5 ,6 ]
Dunn, Kenneth W. [3 ]
Dinauer, Mary C. [1 ,2 ]
机构
[1] Indiana Univ, James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Sch Med, Dept Pediat Hematol Oncol,Dept Microbiol & Immuno, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
[3] Indiana Univ, Med Ctr, Dept Med, Div Nephrol, Indianapolis, IN 46202 USA
[4] Univ Iowa, Dept Med, Inflammat Program, Coralville, IA 52241 USA
[5] Univ Iowa, Dept Microbiol, Coralville, IA 52241 USA
[6] Vet Affairs Med Ctr, Coralville, IA 52241 USA
基金
美国国家卫生研究院;
关键词
CHRONIC GRANULOMATOUS-DISEASE; HUMAN BLOOD PHAGOCYTES; CYTOCHROME-B; SUBCELLULAR-LOCALIZATION; CYTOPLASMIC DOMAIN; RESPIRATORY BURST; HUMAN NEUTROPHILS; FOCAL EXOCYTOSIS; B(558); PHAGOSOME;
D O I
10.4049/jimmunol.0803476
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Flavocvtochrome b(558), the catalytic core of the phagocytic NADPH oxidase, mediates the transfer of electrons from NADPH to molecular oxygen to generate superoxide for host defense. Flavocytochrome b is a membrane heterodimer consisting of a large subunit gp91(phox) (NOX2) and a smaller subunit, p22(phox). Although in neutrophils flavocytochrome b has been shown to localize to the plasma membrane and specific granules, little is known about its distribution in macrophages. Using immunofluorescent staining and live cell imaging of fluorescently tagged gp91(phox) and p22(phox), we demonstrate in a Chinese hamster ovary cell model system and in RAW 264.7 and primary murine bone marrow-derived macrophages that flavocytochrome b is found in the Rab11-positive recycling endocytic compartment, as well as in Rab5-positive early endosomes and plasma membrane. Additionally, we show that unassembled p22(phox) and gp91(phox) subunits localize to the endoplasmic reticulum, which redistribute to the cell surface and endosomal compartments following heterodimer formation. These studies show for the first time that flavocytochrome b localizes to intracellular compartments in macrophages that recycle to the plasma membrane, which may act as a reservoir to deliver flavocytochrome b to the cell surface and phagosome membranes. The Journal of Immunology, 2009, 182: 2325-2339.
引用
收藏
页码:2325 / 2339
页数:15
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