Submitted October 29, 2007
Accepted December 17, 2007
IL6/sIL6R complex contributes to emergency granulopoietic response in G-CSF and GM-CSF deficient mice
Francesca Walker*, Hui-Hua Zhang, Vance Matthews, Janet Weinstock, Edouard C Nice, Matthias Ernst, Stefan Rose-John, and Antony W Burgess
Ludwig Institute for Cancer Research, Melbournce Tumor Biology Branch, Melbourne, Victoria, Australia
JDRF Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia
Biochemisches Institute, Christian-Albrechts-Universitat, Kiel, Germany
* Corresponding author; email: francesca.walker{at}ludwig.edu.au.
Mice defective in both G-CSF and GM-CSF have severely impaired neutrophil production and function, yet these mice respond to acute pathogen challenge with a significant neutrophil response. We have recently reported the development of an in vitro system to detect granulopoietic cytokines secreted from cells isolated from G-CSF, GM-CSF double knockout mice. The conditioned media (CM) produced by these cells after stimulation with LPS or C.albicans supports the production and differentiation of granulocytes, i.e. the CM contains neutrophil promoting activity (NPA). We now show that the NPA in the G-CSF-/-/GM-CSF-/- conditioned media requires IL-6 , is abolished by soluble gp130, and can be specifically immunodepleted by an anti-IL6R antibody. NPA effects on bone marrow cells are also mimicked by Hyper-IL6, and the soluble IL-6 R is present in NPA. These results show that the IL6/sIL6R complex is the major effector of NPA. NPA production by mice defective for both G-CSF and GM-CSF uncovers an alternative pathway to granulocyte production, which is activated following exposure to pathogens.
