Innate Immunity and Mobilization of Hematopoietic Stem Cells

Several mechanisms have been postulated to orchestrate mobilization of hematopoietic stem/progenitor cells (HSPCs), and still more work is needed to better understand this process and to gain better mechanistic insight.

Evidence accumulated that mobilization of HSPCs is a part of innate immunity response to tissue organ injury, stress, and infection. This evolutionary ancient process is orchestrated by granulocytes and monocytes that trigger activation of complement cascade and the coagulation cascade.

We will present data from our laboratory that initiation of complement cascade activation and subsequently activation of the coagulation cascade during mobilization process are dependent on mannan-binding lectin (MBL). The mannan-binding pathway activates MBL-associated serine proteases (MASP-1 and MASP-2) that cleave the third complement component C3 and prothrombin. Cleavage of C3 leads to formation of classical C5 convertase and cleavage of prothrombin generates thrombin, which has "C5-like convertase" activity. Finally, both C5 convertase and thrombin cleave the fifth complement component C5, and activate distal part of the complement cascade that is crucial for egress of HSCPs from bone marrow niches into peripheral blood.