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Increased neutrophil respiratory burst in bcr-null mutants.

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.

Pubmed ID: 7889565

Authors

  • Voncken JW
  • van Schaick H
  • Kaartinen V
  • Deemer K
  • Coates T
  • Landing B
  • Pattengale P
  • Dorseuil O
  • Bokoch GM
  • Groffen J

Journal

Cell

Publication Data

March 10, 1995

Associated Grants

  • Agency: NCI NIH HHS, Id: CA50248
  • Agency: NHLBI NIH HHS, Id: HL 48008

Mesh Terms

  • Actin Cytoskeleton
  • Animals
  • Endotoxins
  • Female
  • GTP-Binding Proteins
  • Gene Targeting
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neutropenia
  • Neutrophil Activation
  • Neutrophils
  • Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcr
  • Respiratory Burst
  • Shock, Septic
  • Superoxides
  • Toxemia
  • rac GTP-Binding Proteins