期刊
LEUKEMIA
卷 26, 期 4, 页码 736-745出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2011.252
关键词
LL-37; SDF-1; CXCR4; C1P; S1P; stem cell homing
资金
- NIH [R01 CA106281-01, R01 DK074720]
- European Union
- KBN [N N401 024536]
- Innovative Economy Operational Program [POIG.01.01.02-00-109/09]
- Henry M and Stella M Hoenig Endowment
- Abraham J and Phyllis Katz Foundation
- Dr Donald and Ruth Weber Goodman Philanthropic Fund
We report that the bone marrow (BM) stroma-released LL-37, a member of the cathelicidin family of antimicrobial peptides, primes/increases the responsiveness of murine and human hematopoietic stem/progenitor cells (HSPCs) to an alpha-chemokine stromal-derived factor-1 (SDF-1) gradient. Accordingly, LL-37 is upregulated in irradiated BM cells and enhances the chemotactic responsiveness of hematopoietic progenitors from all lineages to a low physiological SDF-1 gradient as well as increasing their (i) adhesiveness, (ii) SDF-1-mediated actin polymerization and (iii) MAPK(p42/44) phosphorylation. Mice transplanted with BM cells ex vivo primed by LL-37 showed accelerated recovery of platelet and neutrophil counts by similar to 3-5 days compared with mice transplanted with unprimed control cells. These priming effects were not mediated by LL-37 binding to its receptor and depended instead on the incorporation of the CXCR4 receptor into membrane lipid rafts. We propose that LL-37, which has primarily antimicrobial functions and is harmless to mammalian cells, could be clinically applied to accelerate engraftment as an ex vivo priming agent for transplanted human HSPCs. This novel approach would be particularly important in cord blood transplantations, where the number of HSCs available is usually limited. Leukemia (2012) 26, 736-745; doi:10.1038/leu.2011.252; published online 20 September 2011
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