New insight into the mechanism of granulocyte colony-stimulating factor (G-CSF) that induces the mobilization of neutrophils

Figures & data

Figure 1. Human G-CSF structure.

Figure 2. The scheme proposed for domains and downstream signal pathways of G-CSFR.

Figure 3. [A] In the absence of the ligand, G-CSFR is associated with Janus kinases (Jaks). [B] The binding of the ligand to the receptor occurs at a 2:2 ligand:receptor subunit stoichiometry, forming a crossover configuration between the receptor subunits that brings the Jaks into proximity and enables their trans-phosphorylation and stimulation. [C] The intracellular 4-tyrosine residues of the G-CSFR (represented by stars) are phosphorylated by Jaks. [D] STAT interacts with the phosphotyrosine residues through their Src Homology 2 (SH2) domains and become phosphorylated by the Jak. Phospho-dimers of STATs accumulate in the nucleus and activate transcription factors that drive the neutrophils from the bone marrow to the blood circulation.

Figure 4. Scheme of the proposed model. How G-CSF and STAT3 induce the mobilization of neutrophils. At the early stage of acute inflammation, MIP-2, KC, and their shared receptor CXCR2 induce the mobilization of neutrophils from the BM to the blood circulation. At the late stage of acute inflammation, GCSF, together with STAT3, inhibits CXCR2-mediated rapid neutrophil mobilization and reserved neutrophils in the BM, in part throughout their CXCR4 expression, which binds to SDF-1 (stromal cells express SDF-1) expressed in the BM. (↓ reserve ؛ ↑ induce).