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Stem Cells

The bone marrow-expressed antimicrobial cationic peptide LL-37 enhances the responsiveness of hematopoietic stem progenitor cells to an SDF-1 gradient and accelerates their engraftment after transplantation

Leukemia volume 26, pages 736–745 (2012)Cite this article

Abstract

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 α-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) MAPKp42/44 phosphorylation. Mice transplanted with BM cells ex vivo primed by LL-37 showed accelerated recovery of platelet and neutrophil counts by ∼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.

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Acknowledgements

This work was supported by NIH R01 CA106281-01, NIH R01 DK074720, EU structural funds, a KBN grant (N N401 024536), European Union structural funds, Innovative Economy Operational Program POIG.01.01.02-00-109/09 and the Henry M and Stella M Hoenig Endowment (to MZR), and the Abraham J and Phyllis Katz Foundation and the Dr Donald and Ruth Weber Goodman Philanthropic Fund (to MJL). The authors acknowledge the Cleveland Cord Blood Center and the Cleveland Volunteer Donating Community as the source of the experimental material, and the efforts of the staff at the Cleveland Cord Blood Center.

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Authors and Affiliations

  1. Department of Medicine, Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    W Wu, C H Kim, R Liu, M Kucia, J Ratajczak & M Z Ratajczak

  2. Department of Physiology, Pomeranian Medical University, Szczecin, Poland

    M Kucia, W Marlicz, J Ratajczak & M Z Ratajczak

  3. Cleveland Cord Blood Center, Cleveland, OH, USA

    N Greco

  4. Department of Medicine, Hematopoietic Stem Cell Transplant Program, University of Virginia, Charlottesville, VA, USA

    M J Laughlin

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  1. W Wu
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Correspondence to M Z Ratajczak.

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Wu, W., Kim, C., Liu, R. et al. The bone marrow-expressed antimicrobial cationic peptide LL-37 enhances the responsiveness of hematopoietic stem progenitor cells to an SDF-1 gradient and accelerates their engraftment after transplantation. Leukemia 26, 736–745 (2012). https://doi.org/10.1038/leu.2011.252

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