Immune cells known as neutrophils produce reactive oxygen intermediates (ROIs) to combat infection with microbes that can cause diseases such as pneumonia. New insight into the molecular pathway regulating neutrophil production of ROIs in mice has been provided by Wojciech Swat and colleagues at Washington University School of Medicine, St. Louis.
Several signals are needed to stimulate neutrophils to produce ROIs , including signals generated by neutrophils adhering to the extracellular matrix. In this study, the proteins Vav and PLC-gamma-2 were shown to be essential for neutrophil production of ROIs in response to various adhesion-dependent stimuli.
They were found to be part of a signaling pathway that linked integrin-mediated adhesion to the NADPH oxidase complex that produces ROIs. Importantly, mice lacking Vav were unable to control infection with either Pseudomonas aeruginosa or Staphylococcus aureus, 2 common microbes associated with fatal cases of hospital-acquired pneumonia.
TITLE: Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLC-gamma-2 signaling axis in mice
AUTHOR CONTACT:
Wojciech Swat
Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: (314) 747-8889; Fax: (314) 362-4096