"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 and during an "emergency" situation. Generation of G-CSF and G-CSF receptor-deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted 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-macrophage (GM) and macrophage (M) progenitors were observed in the bone marrow of G-CSF-deficient mice. Of the cytokines surveyed, interleukin (IL)-6 levels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF-deficient mice infected with C albicans than similarly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infected 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 developed absolute neutrophilia and had elevated numbers of GM and M progenitors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promoting the emergency response to candidal infection. (Blood. 2000;95:3725-3733)
Basu
S
S
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, PO Royal Melbourne Hospital, Victoria 3050, Australia. sunanda.basu@ludwig.edu.au
Hodgson
G
G
Zhang
H H
HH
Katz
M
M
Quilici
C
C
Dunn
A R
AR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002176:Candida albicans; D002177:Candidiasis / Q000473:pathology / Q000503:physiopathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006098:Granulocytes / Q000166:cytology / Q000473:pathology*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000473:pathology; D007700:Kinetics; D019891:Leukopoiesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D015850:Interleukin-6; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor