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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2011
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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. |
format | Online Article Text |
id | pubmed-3244577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
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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