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. Author manuscript; available in PMC: 2017 Aug 19.
Published in final edited form as: Adv Exp Med Biol. 2013;735:219–232. doi: 10.1007/978-1-4614-4118-2_15

Figure 3. The involvement of elements of innate immunity in homing and engraftment of HSPCs.

Figure 3

Conditioning for transplantation by radio-chemotherapy induces a proteolytic microenvironment in BM and SDF-1 level due to the induction of proteolytic microenvironment decreases. However, at the same time, BM cells damaged by conditioning for transplantation by lethal irradiation release bioactive lipids (S1P and C1P) that are potent chemoattractants for HSPCs. In addition to S1P and C1P there are also released from damaged cells purines (ATP, UTP) that are endowed with chemotactic activity against HSPCs. Induced by myeloablative treatment BM damage activation of CC leads to release of C3 and C5 cleavage fragments, C3a (1, 5) and C5a respectively, and generation of soluble C5ab-C9 (MAC) (3, 6). While, C3a enhances responsiveness of HSPCs to SDF-1 gradient (1, 5), iC3b deposits on BM endothelium (2), stroma cells and osteoblasts (4) tether HSPCs in CR3-dependent manner. C5a and soluble MAC (C5b-C9) enhance secretion of SDF-1 by stroma cells and secretion of two important antimicrobial cationic peptides by BM stroma cells (cathelicidin [LL-37] and β2-defensin) (7) that similarly as C3a (1, 5) enhance responsiveness of HSPCs to SDF-1 gradient (8). This increase in SDF-1 secretion and increase in responsiveness of HSPCs to SDF-1 gradient ameliorate the drop in SDF-1 level that occurs in highly proteolytic microenvironment of conditioned by radio/chemotherapy BM. Soluble MAC (C5b-C9), in addition to antimicrobial cationic peptides (C3a, LL-37 and β2-defensin) may also enhance responsiveness of HSPCs to SDF-1 gradient (3, 6). In addition to SDF-1 homing of HSPCs is mediated by bioactive lipids (S1P and C1P) and some nucleotides (ATP and UTP) that are released from damaged cells. The potential involvement of CC clevage fragments in modulating BM level of S1P, C1P, ATP and UTP requires further studies.