Fig. 2

Role of inflammasomes in the three stages of HSCT Mobilization. A In the initiation phase, mobilizing agents stimulate the transmembrane protein pannexin-1 in innate immune cells, leading to the release of eATP. eATP subsequently binds to P2X ion channels (P2X1, P2X4, P2X7), causing an influx of K⁺ and an efflux of Ca²⁺, which triggers the activation of inflammasomes and caspase-1. This process also results in the release of various DAMPs, such as IL-1β, IL-18, HMGB1, and S100A9 through GSDMD, thereby creating a positive feedback loop that amplifies inflammation. B During the amplification phase, DAMPs modulate the MBL/MASPs pathway and the alternative complement pathway, triggering the activation of the ComC and CoaC. This results in the production of C3a, C5a, desArgC5a, and the C5b-C9 complex. At this stage, eATP is converted into adenosine by CD39 and CD73, which inhibits mobilization by upregulating HO-1 and iNOS. Pathways promoting mobilization are indicated by red arrows, while the inhibitory pathways associated with adenosine are marked by blue arrows. C In the effector phase, C5a initiates NLRP3 activation in HSPCs, further escalating the inflammatory response. Additionally, these complement molecules enhance granulocyte degranulation, leading to the secretion of hydrolases that weaken the CXCR4-SDF-1 and VLA-4-VCAM-1 axis. S1P is released by the MAC to chemotax HSPCs into peripheral blood vessels. Moreover, lipid rafts are stimulated by increased membrane assembly via the Nox2/ROS/NLRP3 pathway. This process facilitates the integration of CXCR4 and VLA-4 on the plasma membrane, enhancing HSPCs’ sensitivity to environmental signals, thereby promoting their mobilization, homing, and engraftment