Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation.
LPS endotoxin-induced macrophage activation is recognized to be important in both nonspecific immunity and endotoxin-induced sepsis when excessive macrophage stimulation occurs. In this study, we showed that reduction of c-Abl in macrophages prevented LPS-induced growth arrest, nitric oxide production and TNF-alpha secretion by ANA-1 macrophages. These cells continued to grow but later underwent apoptosis. Reduction of c-Abl in these cells led to reduced c-Abl kinase activity associated with Ran, which recently has been shown to be an LPS-responsive gene product. Our data suggest that c-Abl tyrosine kinase is one of the intermediates downstream of the initial signal transduction event related to activation of macrophages by LPS.
Le
Q
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Daniel
R
R
Chung
S W
SW
Kang
A D
AD
Eisenstein
T K
TK
Sultzer
B M
BM
Simpkins
H
H
Wong
P M
PM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002461:Cell Line, Transformed; D005822:Genetic Vectors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis / Q000502:physiology*; D014162:Transfection / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl