title: Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation.
abstract: 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.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Le
authors.forename: R
authors.initials: R
authors.lastname: Daniel
authors.forename: S W
authors.initials: SW
authors.lastname: Chung
authors.forename: A D
authors.initials: AD
authors.lastname: Kang
authors.forename: T K
authors.initials: TK
authors.lastname: Eisenstein
authors.forename: B M
authors.initials: BM
authors.lastname: Sultzer
authors.forename: H
authors.initials: H
authors.lastname: Simpkins
authors.forename: P M
authors.initials: PM
authors.lastname: Wong
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl