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BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION

We report that the bone marrow stroma-released LL-37, a member of the cathelicidin family of antimicrobial peptides, primes/increases 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 upre...

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Autores principales: Wu, Wan, Kim, Chi Hwa, Liu, Rui, Kucia, Magda, Greco, Nicholas, Ratajczak, Janina, Laughlin, Mary L., Ratajczak, Mariusz Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244577/
https://www.ncbi.nlm.nih.gov/pubmed/21931324
http://dx.doi.org/10.1038/leu.2011.252
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author Wu, Wan
Kim, Chi Hwa
Liu, Rui
Kucia, Magda
Greco, Nicholas
Ratajczak, Janina
Laughlin, Mary L.
Ratajczak, Mariusz Z.
author_facet Wu, Wan
Kim, Chi Hwa
Liu, Rui
Kucia, Magda
Greco, Nicholas
Ratajczak, Janina
Laughlin, Mary L.
Ratajczak, Mariusz Z.
author_sort Wu, Wan
collection PubMed
description We report that the bone marrow stroma-released LL-37, a member of the cathelicidin family of antimicrobial peptides, primes/increases 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 increases their i) adhesiveness, ii) SDF-1-mediated actin polymerization, and iii) MAPKp42/44 phosphorylation. Mice transplanted with bone marrow (BM) cells ex vivo primed by LL-37 showed accelerated recovery of platelet and neutrophil counts by ~3–5 days compared to mice transplanted with unprimed control cells. These priming effects were not mediated by LL-37 binding to its receptor and depended instead on 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 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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spelling pubmed-32445772012-10-01 BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION Wu, Wan Kim, Chi Hwa Liu, Rui Kucia, Magda Greco, Nicholas Ratajczak, Janina Laughlin, Mary L. Ratajczak, Mariusz Z. Leukemia Article We report that the bone marrow stroma-released LL-37, a member of the cathelicidin family of antimicrobial peptides, primes/increases 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 increases their i) adhesiveness, ii) SDF-1-mediated actin polymerization, and iii) MAPKp42/44 phosphorylation. Mice transplanted with bone marrow (BM) cells ex vivo primed by LL-37 showed accelerated recovery of platelet and neutrophil counts by ~3–5 days compared to mice transplanted with unprimed control cells. These priming effects were not mediated by LL-37 binding to its receptor and depended instead on 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 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. 2011-09-20 2012-04 /pmc/articles/PMC3244577/ /pubmed/21931324 http://dx.doi.org/10.1038/leu.2011.252 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wu, Wan
Kim, Chi Hwa
Liu, Rui
Kucia, Magda
Greco, Nicholas
Ratajczak, Janina
Laughlin, Mary L.
Ratajczak, Mariusz Z.
BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title_full BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title_fullStr BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title_full_unstemmed BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title_short BONE MARROW EXPRESSED ANTIMICROBIAL CATIONIC PEPTIDE LL-37 ENHANCES RESPONSIVENESS OF HEMATOPOIETIC STEM PROGENITOR CELLS TO AN SDF-1 GRADIENT AND ACCELERATES THEIR ENGRAFTMENT AFTER TRANSPLANTATION
title_sort bone marrow expressed antimicrobial cationic peptide ll-37 enhances responsiveness of hematopoietic stem progenitor cells to an sdf-1 gradient and accelerates their engraftment after transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244577/
https://www.ncbi.nlm.nih.gov/pubmed/21931324
http://dx.doi.org/10.1038/leu.2011.252
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