How do red blood cells know when to die?

Author:

Arias Clemente Fernandez12ORCID,Arias Cristina Fernandez3

Affiliation:

1. Departamento de Matemática Aplicada, Universidad Complutense de Madrid, Spain

2. Grupo Interdisciplinar de Sistemas Complejos, Madrid, Spain

3. HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA

Abstract

Human red blood cells (RBCs) are normally phagocytized by macrophages of splenic and hepatic sinusoids at 120 days of age. The destruction of RBCs is ultimately controlled by antagonist effects of phosphatidylserine (PS) and CD47 on the phagocytic activity of macrophages. In this work, we introduce a conceptual model that explains RBC lifespan as a consequence of the dynamics of these molecules. Specifically, we suggest that PS and CD47 define a molecular algorithm that sets the timing of RBC phagocytosis. We show that significant changes in RBC lifespan described in the literature can be explained as alternative outcomes of this algorithm when it is executed in different conditions of oxygen availability. The theoretical model introduced here provides a unified framework to understand a variety of empirical observations regarding RBC biology. It also highlights the role of RBC lifespan as a key element of RBC homeostasis.

Publisher

The Royal Society

Subject

Multidisciplinary

Reference89 articles.

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