PI3K? plays a critical role in neutrophil activation by immune complexes
12.04.2011
Kulkarni S, Sitaru C, Jakus Z, Anderson KE, Damoulakis G, Davidson K, Hirose M, Juss J, Oxley D, Chessa TA, Ramadani F, Guillou H, Segonds-Pichon A, Fritsch A, Jarvis GE, Okkenhaug K, Ludwig R, Zillikens D, Mocsai A, Vanhaesebroeck B, Stephens LR, Hawkins PT.
Sci Signal. 2011;4(168):ra23
Neutrophils may be activated by IgG-containing immune complexes through their Fc?Rs, which has clinical relevance in the setting of inflammatory and autoimmune diseases. In the present study, we used genetic and pharmacological approaches to define a selective role for the ? isoform of phosphoinositide 3-kinase (PI3K?) in Fc?R-dependent activation ex vivo and in animal models. In addition to showing reduced production of reactive oxygen species ex vivo, PI3K?-deficient mice showed different degrees of protection from tissue damage in Fc?R-dependent models of autoantibody-induced skin blistering and of inflammatory arthritis. Therefore, PI3K? emerges as a potential therapeutic target in inflammatory disease.
