A Pivotal Role of Activation of Complement Cascade (CC) in Mobilization of Hematopoietic Stem/Progenitor Cells (HSPC)

Complement cascade (CC) and innate immunity emerge as important and underappreciated modulators of trafficking of hematopoietic stem/progenitor cells (HSPC). Accordingly, we reported that (i) C becomes activated in bone marrow (BM) during G-CSF-induced mobilization by the classical immunoglobulin (Ig)-dependent pathway, and that (ii) C3 cleavage fragments increase the responsiveness of HSPC to an stromal derived factor-1 (SDF-I) gradient. Furthermore, our recent data in immunodeficient mice support the concept that the CC is a major factor modulating egress of HSPC from bone marrow (BM) into peripheral blood (PB). Thus, in light of these findings, mobilization of HSPC could be envisioned as part of an immune response that requires CC activation by the classical Ig-dependent and/or Ig-independent pathways. Hence modulation of CC activation could allow for the development of more efficient mobilization strategies in patients who are poor mobilizers of HSPC.