Spinal cord injury causes chronic bone marrow failure
| العنوان: | Spinal cord injury causes chronic bone marrow failure |
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| المؤلفون: | Faith H. Brennan, Phillip G. Popovich, Jessica M. Marbourg, Katherine A. Mifflin, Adrienne M. Dorrance, Xiaokui M. Mo, Randall S. Carpenter, Matthew H. Burke, Roselyn R. Jiang, Jodie C. E. Hall, Malith Karunasiri |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Benzylamines, Chemokine, Neuroimmunology, General Physics and Astronomy, Cyclams, CXCR4, Mice, 0302 clinical medicine, Bone Marrow, Heterocyclic Compounds, Mice, Inbred NOD, lcsh:Science, Spinal cord injury, Multidisciplinary, biology, Haematopoietic stem cells, Haematopoiesis, medicine.anatomical_structure, Female, Signal Transduction, medicine.drug, Receptors, CXCR4, Science, Bone Marrow Cells, Mice, Transgenic, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, Progenitor cell, Spinal Cord Injuries, Cell Proliferation, business.industry, Plerixafor, Bone marrow failure, General Chemistry, Bone Marrow Failure Disorders, Hematopoietic Stem Cells, medicine.disease, Chemokine CXCL12, Hematopoiesis, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, biology.protein, Cancer research, lcsh:Q, Bone marrow, business, 030217 neurology & neurosurgery |
| الوصف: | 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. Spinal cord injury (SCI) often leads to immune dysfunction, but mechanistic insights are still lacking. Here the authors show that SCI alters chemokine signaling and induces long, persisting defects in hematopoietic stem and progenitor cell migration, thereby entrapping them in the bone marrow and disrupting peripheral immune homeostasis. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::695b8933c6963bee584db1b8eec7b679 https://doi.org/10.1038/s41467-020-17564-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....695b8933c6963bee584db1b8eec7b679 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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