Granulopoiesis (Schalm 41) Flashcards
As neutrophils mature they decrease expression of what receptors, allowing release into the circulation?
CXCR4
Which transcription factor is activated in differentiation of MPPs to CMPs?
PU.1
PU.1 and expression of C/EBP-a promotes transition of CMPs to …
GMPs (Granulocyte/monocyte progenitors)
Continued presence of C/EBP-a and diminished expression of PU.1 results in formation of …
Early neutrophil precursors (from GMPs)
GMPs that maintain high PU.1 and do not express C/EBP-a are committed to …
Monocyte production
C/EBP-a,e; PU.1, and GFI-1 are key in maturation of …
Neutrophils and for gelatinase and secretory vesicle formation
“Emergency” granulopoiesis requires which transcription factor, which is not downregulated by inflammatory cytokines?
C/EBP-b
Continued high levels of C/EBP-a with expression of GATA-1 allows differention of GMPs to …
EoPs
BMCP formation from GMPs requires expression of ___ and inactivation of ___
Expression of GATA 2
Inactivation of C/EBP-a
How does Stem Cell Factor (SCF) affect cell cycle?
Inhibits apoptosis
Promotes entry of cells into the S phase of the cell cycle
Potentiates effects of other cytokines
GM-CSF promotes proliferation and maturation of _____ by inhibiting ______
Granulocytes and macrophages
Inhibits apoptosis
What is the receptor for stem cell factor? Expression of this receptor declines on all granulocytic lineages except…
CD117 (c-kit)
Mast Cells
Name three cell lineages that produce GM-CSF
Macrophages
T-cells and B-cells
Neutrophils
Eosinophils
Mast Cells
Endothelial cells
Bone marrow stromal cells
Osteoblasts
Fibroblasts
Name three effects of G-CSF on neutrophil lineage
Stimulation of survival
Proliferation
Terminal differentiation
Give three control mechanisms of G-CSF production
Macrophages produce IL-23 (decreased with neutrophil phagocytosis) -> IL17 by Th17 lymph’s and NKs -> G-CSF and GM-CSF by endothelial and stromal cells
IL-17 through TLR signaling in the gut/gut microbiome
Induction by TNF-a, IL-1b, and IL-17 in inflammation
Possibly direct sensing of pathogen associated molecular patterns (PAMPs)
IL-6 may work alone or synergistically with G-CSF to mediate…
Bone marrow granulocytic hyperplasia
What is the basal bone marrow transit time for neutrophils in dogs, cats, and horses? In which species are neutrophils mature but are held in the marrow for one additional day?
6 days
held for one additional day in calves
What are the three main cytokines driving neutrophil production?
IL-3, G-CSF, and IL-6
What are the three main cytokines driving eosinophil differentiation?
IL-3, GM-CSF, and IL-5
What is basal production rate of eosinophils?
2-6 days
What is the basal transit time for basophils?
2-3 days
A lineage specific proliferation factor has not been found for which granulocyte? What are some of their growth factors?
Basophils
IL-3, GM-CSF
IL-5
NGF, TGF-b
Migrating mast cell progenitors lack what features?
Mature granules
High-affinity receptors for Fc portion of IgE
What are the primary growth factors for mast cell development?
IL-3
SCF (to c-kit/CD117)
