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.