How the spleen reshapes and retains young and old red blood cells: A computational investigation.

The spleen, the largest secondary lymphoid organ in humans, not only fulfils a broad range of immune functions, but also plays an important role in red blood cell's (RBC) life cycle. Although much progress has been made to elucidate the critical biological processes involved in the maturation o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	He Li, Zixiang Leonardo Liu, Lu Lu, Pierre Buffet, George Em Karniadakis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/71f66109fb344288816c3df2ccba5a47
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:71f66109fb344288816c3df2ccba5a47
record_format	dspace
spelling	oai:doaj.org-article:71f66109fb344288816c3df2ccba5a472021-12-02T19:57:40ZHow the spleen reshapes and retains young and old red blood cells: A computational investigation.1553-734X1553-735810.1371/journal.pcbi.1009516https://doaj.org/article/71f66109fb344288816c3df2ccba5a472021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009516https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The spleen, the largest secondary lymphoid organ in humans, not only fulfils a broad range of immune functions, but also plays an important role in red blood cell's (RBC) life cycle. Although much progress has been made to elucidate the critical biological processes involved in the maturation of young RBCs (reticulocytes) as well as removal of senescent RBCs in the spleen, the underlying mechanisms driving these processes are still obscure. Herein, we perform a computational study to simulate the passage of RBCs through interendothelial slits (IES) in the spleen at different stages of their lifespan and investigate the role of the spleen in facilitating the maturation of reticulocytes and in clearing the senescent RBCs. Our simulations reveal that at the beginning of the RBC life cycle, intracellular non-deformable particles in reticulocytes can be biomechanically expelled from the cell upon passage through IES, an insightful explanation of why this peculiar "pitting" process is spleen-specific. Our results also show that immature RBCs shed surface area by releasing vesicles after crossing IES and progressively acquire the biconcave shape of mature RBCs. These findings likely explain why RBCs from splenectomized patients are significantly larger than those from nonsplenectomized subjects. Finally, we show that at the end of their life span, senescent RBCs are not only retained by IES due to reduced deformability but also become susceptible to mechanical lysis under shear stress. This finding supports the recent hypothesis that transformation into a hemolyzed ghost is a prerequisite for phagocytosis of senescent RBCs. Altogether, our computational investigation illustrates critical biological processes in the spleen that cannot be observed in vivo or in vitro and offer insights into the role of the spleen in the RBC physiology.He LiZixiang Leonardo LiuLu LuPierre BuffetGeorge Em KarniadakisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 11, p e1009516 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 He Li Zixiang Leonardo Liu Lu Lu Pierre Buffet George Em Karniadakis How the spleen reshapes and retains young and old red blood cells: A computational investigation.
description	The spleen, the largest secondary lymphoid organ in humans, not only fulfils a broad range of immune functions, but also plays an important role in red blood cell's (RBC) life cycle. Although much progress has been made to elucidate the critical biological processes involved in the maturation of young RBCs (reticulocytes) as well as removal of senescent RBCs in the spleen, the underlying mechanisms driving these processes are still obscure. Herein, we perform a computational study to simulate the passage of RBCs through interendothelial slits (IES) in the spleen at different stages of their lifespan and investigate the role of the spleen in facilitating the maturation of reticulocytes and in clearing the senescent RBCs. Our simulations reveal that at the beginning of the RBC life cycle, intracellular non-deformable particles in reticulocytes can be biomechanically expelled from the cell upon passage through IES, an insightful explanation of why this peculiar "pitting" process is spleen-specific. Our results also show that immature RBCs shed surface area by releasing vesicles after crossing IES and progressively acquire the biconcave shape of mature RBCs. These findings likely explain why RBCs from splenectomized patients are significantly larger than those from nonsplenectomized subjects. Finally, we show that at the end of their life span, senescent RBCs are not only retained by IES due to reduced deformability but also become susceptible to mechanical lysis under shear stress. This finding supports the recent hypothesis that transformation into a hemolyzed ghost is a prerequisite for phagocytosis of senescent RBCs. Altogether, our computational investigation illustrates critical biological processes in the spleen that cannot be observed in vivo or in vitro and offer insights into the role of the spleen in the RBC physiology.
format	article
author	He Li Zixiang Leonardo Liu Lu Lu Pierre Buffet George Em Karniadakis
author_facet	He Li Zixiang Leonardo Liu Lu Lu Pierre Buffet George Em Karniadakis
author_sort	He Li
title	How the spleen reshapes and retains young and old red blood cells: A computational investigation.
title_short	How the spleen reshapes and retains young and old red blood cells: A computational investigation.
title_full	How the spleen reshapes and retains young and old red blood cells: A computational investigation.
title_fullStr	How the spleen reshapes and retains young and old red blood cells: A computational investigation.
title_full_unstemmed	How the spleen reshapes and retains young and old red blood cells: A computational investigation.
title_sort	how the spleen reshapes and retains young and old red blood cells: a computational investigation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/71f66109fb344288816c3df2ccba5a47
work_keys_str_mv	AT heli howthespleenreshapesandretainsyoungandoldredbloodcellsacomputationalinvestigation AT zixiangleonardoliu howthespleenreshapesandretainsyoungandoldredbloodcellsacomputationalinvestigation AT lulu howthespleenreshapesandretainsyoungandoldredbloodcellsacomputationalinvestigation AT pierrebuffet howthespleenreshapesandretainsyoungandoldredbloodcellsacomputationalinvestigation AT georgeemkarniadakis howthespleenreshapesandretainsyoungandoldredbloodcellsacomputationalinvestigation
_version_	1718375783719763968

How the spleen reshapes and retains young and old red blood cells: A computational investigation.

Ejemplares similares