Figure 7. Novel mechanistic insight into BM HSPC mobilization.

HSPCs are actively retained in BM and retention signals in the BM niches counteract a S1P-mediated chemotactic plasma gradient. Mobilizing agents disrupt major HSPC-anchoring signals (i.e., CXCR4-SDF-1 and VLA4-VCAM-1 interactions) and release HSPCs from their niches (Step I). First, as reported previously¹⁶,²⁰,⁵¹ activated granulocytes egress from BM into sinusoids in response to C5 cleavage fragments and thus pave the way for HSPC (Step II). Next, MAC generated in the final step of CC activation enhances release of S1P from erythrocytes into the plasma, and the plasma S1P level directs egress of HSPCs into PB (Step III).