Inhibition of the neutrophil NADPH oxidase by adenosine is associated with increased movement of flavocytochrome b between subcellular fractions.
Adenosine is a potent inhibitor of reactive oxygen species (ROS) production by the NADPH oxidase in fMLF-stimulated neutrophils. Although much is known about the pharamacology and signal transduction of this effect, it is not known how adenosine affects assembly and localization of the NADPH oxidase components within the neutrophil. We report here that adenosine pretreatment of fMLF-stimulated neutrophils results in decreased plasma membrane/secretory granule content of the flavocytochrome b components (p22phox and gp91phox) of the NADPH oxidase, which correlates with inhibition of ROS production. Adenosine treatment did not affect upregulation of secretory and specific granule surface markers, confirming that degranulation was not impaired by adenosine. However, adenosine treatment did result in increased movement of cell-surface flavocytochrome b to heavy granule fractions in fMLF-stimulated neutrophils. These data suggest that adenosine-mediated effects on neutrophil ROS production are due, in part to endocytosis and/or redistribution of flavocytochrome b between various subcellular compartments.
Swain
Steve D
SD
Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Siemsen
Daniel W
DW
Nelson
Laura K
LK
Sipes
Karen M
KM
Hanson
Angela J
AJ
Quinn
Mark T
MT
D000241:Adenosine / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D045303:Cytochromes b / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D026901:Membrane Transport Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009252:NADPH Dehydrogenase / Q000032:analysis / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism*
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D045303:Cytochromes b; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D000241:Adenosine