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 neutro...

Full description

Saved in:
Bibliographic Details
Published inCell Vol. 80; no. 5; pp. 719 - 728
Main Authors Voncken, Jan Willem, Schaick, Hermien van, Kaartinen, Vesa, Deemer, Kathleen, Coates, Thomas, Landing, Benjamin, Pattengale, Paul, Dorseuil, Olivier, Bokoch, Gary M, Groffen, John, Heisterkamp, Nora
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 10.03.1995
Subjects
Actin Cytoskeleton - physiology
Animals
Endotoxins - toxicity
Female
Gene Targeting
GTP-Binding Proteins - biosynthesis
GTP-Binding Proteins - metabolism
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
Mutation - physiology
Neutropenia - chemically induced
Neutropenia - immunology
Neutrophil Activation
Neutrophils - metabolism
Oncogene Proteins - genetics
Oncogene Proteins - physiology
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcr
rac GTP-Binding Proteins
Respiratory Burst - immunology
Shock, Septic - chemically induced
Shock, Septic - immunology
Shock, Septic - pathology
Superoxides - metabolism
Toxemia - chemically induced
Toxemia - immunology
Toxemia - pathology
Online AccessGet full text

Cover

More Information
Summary: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 p21 rac2 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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(95)90350-X