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Spinal cord injury causes chronic bone marrow failure

Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marro...

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Autores principales: Carpenter, Randall S., Marbourg, Jessica M., Brennan, Faith H., Mifflin, Katherine A., Hall, Jodie C. E., Jiang, Roselyn R., Mo, Xiaokui M., Karunasiri, Malith, Burke, Matthew H., Dorrance, Adrienne M., Popovich, Phillip G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382469/
https://www.ncbi.nlm.nih.gov/pubmed/32710081
http://dx.doi.org/10.1038/s41467-020-17564-z
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author Carpenter, Randall S.
Marbourg, Jessica M.
Brennan, Faith H.
Mifflin, Katherine A.
Hall, Jodie C. E.
Jiang, Roselyn R.
Mo, Xiaokui M.
Karunasiri, Malith
Burke, Matthew H.
Dorrance, Adrienne M.
Popovich, Phillip G.
author_facet Carpenter, Randall S.
Marbourg, Jessica M.
Brennan, Faith H.
Mifflin, Katherine A.
Hall, Jodie C. E.
Jiang, Roselyn R.
Mo, Xiaokui M.
Karunasiri, Malith
Burke, Matthew H.
Dorrance, Adrienne M.
Popovich, Phillip G.
author_sort Carpenter, Randall S.
collection PubMed
description Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marrow hematopoietic stem and progenitor cells (HSPC), but these cells cannot leave the bone marrow, even after challenging the host with a potent inflammatory stimulus. Sequestration of HSPCs in bone marrow after SCI is linked to aberrant chemotactic signaling that can be reversed by post-injury injections of Plerixafor (AMD3100), a small molecule inhibitor of CXCR4. Even though Plerixafor liberates HSPCs and mature immune cells from bone marrow, competitive repopulation assays show that the intrinsic long-term functional capacity of HSPCs is still impaired in SCI mice. Together, our data suggest that SCI causes an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction.
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spelling pubmed-73824692020-07-28 Spinal cord injury causes chronic bone marrow failure Carpenter, Randall S. Marbourg, Jessica M. Brennan, Faith H. Mifflin, Katherine A. Hall, Jodie C. E. Jiang, Roselyn R. Mo, Xiaokui M. Karunasiri, Malith Burke, Matthew H. Dorrance, Adrienne M. Popovich, Phillip G. Nat Commun Article Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marrow hematopoietic stem and progenitor cells (HSPC), but these cells cannot leave the bone marrow, even after challenging the host with a potent inflammatory stimulus. Sequestration of HSPCs in bone marrow after SCI is linked to aberrant chemotactic signaling that can be reversed by post-injury injections of Plerixafor (AMD3100), a small molecule inhibitor of CXCR4. Even though Plerixafor liberates HSPCs and mature immune cells from bone marrow, competitive repopulation assays show that the intrinsic long-term functional capacity of HSPCs is still impaired in SCI mice. Together, our data suggest that SCI causes an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction. Nature Publishing Group UK 2020-07-24 /pmc/articles/PMC7382469/ /pubmed/32710081 http://dx.doi.org/10.1038/s41467-020-17564-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Carpenter, Randall S.
Marbourg, Jessica M.
Brennan, Faith H.
Mifflin, Katherine A.
Hall, Jodie C. E.
Jiang, Roselyn R.
Mo, Xiaokui M.
Karunasiri, Malith
Burke, Matthew H.
Dorrance, Adrienne M.
Popovich, Phillip G.
Spinal cord injury causes chronic bone marrow failure
title Spinal cord injury causes chronic bone marrow failure
title_full Spinal cord injury causes chronic bone marrow failure
title_fullStr Spinal cord injury causes chronic bone marrow failure
title_full_unstemmed Spinal cord injury causes chronic bone marrow failure
title_short Spinal cord injury causes chronic bone marrow failure
title_sort spinal cord injury causes chronic bone marrow failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382469/
https://www.ncbi.nlm.nih.gov/pubmed/32710081
http://dx.doi.org/10.1038/s41467-020-17564-z
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