Sepsis Alters the Megakaryocyte–Platelet Transcriptional Axis Resulting in Granzyme B–mediated Lymphotoxicity
| العنوان: | Sepsis Alters the Megakaryocyte–Platelet Transcriptional Axis Resulting in Granzyme B–mediated Lymphotoxicity |
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| المؤلفون: | Reecha Sachdeva, Svetlana Ghimbovschi, Lindsay M. Debiase, Margaret K. Bradbury, Ervand Kristosturyan, Bahar Mojgani, JoAnne E Natale, Joanna S. Cohen, Andrew A. Wiles, Andrew J. Degnan, Wai Man Ngor, Matthew Chow, Matthew Sharron, Robert J. Freishtat, Eric P. Hoffman, Clarice Bunag, Angela S. Benton |
| المصدر: | American Journal of Respiratory and Critical Care Medicine. 179:467-473 |
| بيانات النشر: | American Thoracic Society, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Blood Platelets, Male, Pulmonary and Respiratory Medicine, Adolescent, Apoptosis, Spleen, Critical Care and Intensive Care Medicine, Severity of Illness Index, Granzymes, Sepsis, Mice, C. Critical Care, Megakaryocyte, Intensive care, medicine, Animals, Humans, Cytotoxic T cell, Platelet, RNA, Messenger, Child, biology, business.industry, Infant, medicine.disease, Granzyme B, medicine.anatomical_structure, Granzyme, Child, Preschool, Immunology, biology.protein, Female, business, Megakaryocytes |
| الوصف: | Sepsis-related mortality results in part from immunodeficiency secondary to profound lymphoid apoptosis. The biological mechanisms responsible are not understood.Because recent evidence shows that platelets are involved in microvascular inflammation and that they accumulate in lymphoid microvasculature in sepsis, we hypothesized a direct role for platelets in sepsis-related lymphoid apoptosis.We studied megakaryocytes and platelets from a murine-induced sepsis model, with validation in septic children, which showed induction of the cytotoxic serine protease granzyme B.Platelets from septic mice induced marked apoptosis of healthy splenocytes ex vivo. Platelets from septic granzyme B null (-/-) mice showed no lymphotoxicity.Our findings establish a conceptual advance in sepsis: Septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B. Given the contribution of lymphoid apoptosis to sepsis-related mortality, modulation of platelet granzyme B becomes an important new target for investigation and therapy. |
| تدمد: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200807-1085oc |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d8b11f718575ee079927814904b55172 https://doi.org/10.1164/rccm.200807-1085oc |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d8b11f718575ee079927814904b55172 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354970 1073449X |
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| DOI: | 10.1164/rccm.200807-1085oc |