title: Increased neutrophil respiratory burst in bcr-null mutants.
abstract: Philadelphia (Ph)-positive leukemias invariably contain a chromosomal translocation fusing BCR to ABL. The BCR-ABL protein is responsible for leukemogenesis. Here we show that exposure of bcr-null mutant mice to gram-negative endotoxin led to severe septic shock and increased tissue injury by neutrophils. Neutrophils of bcr (-/-) mice showed a pronounced increase in reactive oxygen metabolite production upon activation and were more sensitive to priming stimuli. Activated (-/-) neutrophils displayed a 3-fold increased p21rac2 membrane translocation compared with (+/+) neutrophils. These results connect Bcr in vivo with the regulation of Rac-mediated superoxide production by the NADPH-oxidase system of leukocytes and suggest a link between Bcr function and the cell type affected in Ph-positive leukemia.
authors.affiliation: Department of Pathology, Childrens Hospital of Los Angeles 90027.
authors.forename: J W
authors.initials: JW
authors.lastname: Voncken
authors.forename: H
authors.initials: H
authors.lastname: van Schaick
authors.forename: V
authors.initials: V
authors.lastname: Kaartinen
authors.forename: K
authors.initials: K
authors.lastname: Deemer
authors.forename: T
authors.initials: T
authors.lastname: Coates
authors.forename: B
authors.initials: B
authors.lastname: Landing
authors.forename: P
authors.initials: P
authors.lastname: Pattengale
authors.forename: O
authors.initials: O
authors.lastname: Dorseuil
authors.forename: G M
authors.initials: GM
authors.lastname: Bokoch
authors.forename: J
authors.initials: J
authors.lastname: Groffen
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D018390:Gene Targeting; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000502:physiology*; D009503:Neutropenia / Q000139:chemically induced / Q000276:immunology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D016897:Respiratory Burst / Q000276:immunology*; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D014115:Toxemia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D020744:rac GTP-Binding Proteins
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D013481:Superoxides; D011505:Protein-Tyrosine Kinases; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins