C/EBPβ Is Involved in the Amplification of Early Granulocyte Precursors during Candidemia-Induced “Emergency” Granulopoiesis

Abstract

Granulopoiesis is tightly regulated to meet host demands during both “steady-state” and “emergency” situations, such as infections. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPβ is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1–5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPβ was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPβ knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPβ is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.

Gr-1dimCD11b+ Immature Myeloid-Derived Suppressor Cells but Not Neutrophils Are Markers of Lethal Tuberculosis Infection in Mice

“…1C and 2A). Previously, several authors have demonstrated that the levels of Gr-1 and Ly-6G expression are indicative of a degree of granulocytic cell differentiation and maturation (14, 30). We, therefore, compared the phenotype of CD11b + that in infected mice expressed Gr-1 at different levels, i.e., Gr-1 dim and “Gr-1 hi ” cells (Fig.…”

“…As discussed above, the levels of Ly-6G and Gr-1 expression are indicative of a degree of myeloid cell differentiation and maturation (14, 30). We therefore assessed whether in our model there was an association between TB progression and the levels of Gr-1 expression by the whole population of CD11b + cells.…”

Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes

“…FACS analysis revealed an increased frequency of c-Kit int Gr1 low cells, previously identified as myelocytes and metamyelocytes (MC-MMs) ( Figure 3F). 28 Both frequency and absolute count of more mature myeloid cells, characterized by loss of c-Kit expression and bright Gr1 staining, were lower, suggesting an arrest of lineage progression at the MC-MM stage. Morphological assessment of the bone marrow confirmed that terminal granulopoiesis is severely affected in Sbds f/f recipients, with accumulation of MC-MMs and reduced frequency of segmented neutrophils ( Figure 3G and Online Supplementary Figure S3).…”

Changes in Gene Expression during G-CSF–Induced Emergency Granulopoiesis in Humans

“…Satake et al (20) examined the effect of candidemia-induced emergency granulopoiesis in mice and found no difference in the mRNA expression profiles of Mpo, Ctsg, Ltf, and Mmp9 in neutrophil precursors (MB to PMN) compared with the steady state (20). They did find an increase in C/EBPb protein, but not mRNA, indicating that C/EBPb is not regulated on a transcriptional level from the MB stage and onward (20). These results corroborate our findings that transcription of most genes encoding granule proteins as well as of CEBPB is unaffected by emergency granulopoiesis in humans.…”