"Emergency" granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state a nd during an "emergency" situation. Generation of G-CSF and G-CSF receptor- deficient mice by gene targeting has demonstrated unequivocally the importa nce of G-CSF in the regulation of baseline granulopoiesis, This study attem pted to define the physiologic role of G-CSF during an emergency situation by challenging a cohort of wild-type and G-CSF-deficient mice with Candida albicans, Interestingly, after infection, G-CSF-deficient mice developed an absolute neutrophilia that was observed both in blood and bone marrow. In addition, 3 days after Candida infection increased numbers of granulocyte-m acrophage(GM) and macrophage (M) progenitors were observed in the bone marr ow of G-CSF-deficient mice. Of the cytokines surveyed, interleukin (IL)-6 l evels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF-deficient mice infected with C albicans than simil arly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infe cted IL-6-deficient mice, or mice simultaneously deficient in G-CSF and IL- 6, developed neutrophilia. Similarly, mice lacking both G-CSF and GM-CSF de veloped absolute neutrophilia and had elevated numbers of GM and M progenit ors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promotin g the emergency response to candidal infection. (C) 2000 by The American So ciety of Hematology.