Figure 1.

A. Interplay between purinergic signaling and ComC activation during mobilization of HSPCs. Pro-mobilizing agent (e.g., G-CSF) activates Gr-1+ cells to secrete proteolytic and lipolytic enymes as well as several DAMPs including: ATP, HGMB1 and S100. While HGMB1 and S100 proteins activate complement cascade (ComC) in MBL-dependent pathway, ATP interacts with P2X7 and P2Y purinergic receptors on hematopoietic cells what leads to activation of inflammasome and release of PLC-β2. Both inflammasome and PLC-β2 promote the effective mobilization. At the same time ATP is processed by CD39 and CD73 ectonucleotidases to adenosine, that inhibits the mobilization process by upregulating in HSPCs heme oxygenase-1 (HO-1). ComC activated in MBL-dependent pathway together with CoaC is crucial in the executing egress of HSPCs from BM into PB. Pathways promoting mobilization are shown by red arrows, and adenosine inhibitory pathway by black arrow. B. Activation of complement cascade and release of C5a after administration of DAMPs (ATP + HGMB1 + S100). C5a level has been measured in PB by employing sensitive ELISA assay. *p < 0.001. C. Administration of DAMPs enhances mobilization of HSPCs in mice. Mononuclear cells (MNCs) were isolated from WT mice mobilized for 6 days with G-CSF alone (control) and 6 days with G-CSF + cocktail of DAMPs (ATP + HGMB1 + S100). The numbers of WBCs, SKL (Sca-1+ /c-kit+ /Lin− ) cells, HSCs (Sca-1+ /CD45+ /Lin− ), and CFU-GM clonogenic progenitors were evaluated in PB. Results from two independent experiments are pooled together. *p < 0.001.