Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation.
In steady-state hematopoiesis, G-CSF (granulocyte-colony stimulating factor) regulates the level of neutrophils in the bone marrow and blood. In this study, we have exploited the availability of G-CSF-deficient mice to evaluate the role of G-CSF in steady-state granulopoiesis and the release of granulocytes from marrow into circulation. The thymidine analogue bromodeoxyuridine (BrdU) was used to label dividing bone marrow cells, allowing us to follow the release of granulocytes into circulation. Interestingly, the labeling index and the amount of BrdU incorporated by blast cells in bone marrow was greater in G-CSF-deficient mice than in wild-type mice. In blood, 2 different populations of BrdU-positive granulocytes, BrdU(bright) and BrdU(dim), could be detected. The kinetics of release of the BrdU(bright) granulocytes from bone marrow into blood was similar in wild-type and G-CSF-deficient mice; however, BrdU(dim) granulocytes peaked earlier in G-CSF-deficient mice. Our findings suggest that the mean transit time of granulocytes through the postmitotic pool is similar in G-CSF-deficient and control mice, although the transit time through the mitotic pool is reduced in G-CSF-deficient mice. Moreover, the reduced numbers of granulocytes that characterize G-CSF-deficient mice is primarily due to increased apoptosis in cells within the granulocytic lineage. Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation.
Molecular Biology Laboratory, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia. sunanda.basu@ludwig.edu.au
Sunanda
S
Basu
George
G
Hodgson
Melissa
M
Katz
Ashley R
AR
Dunn
D000818:Animals; D001773:Blood Cells; D001854:Bone Marrow Cells / Q000166:cytology*; D001973:Bromodeoxyuridine; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D019891:Leukopoiesis / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects
D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine