Vesiculation of Red Blood Cells in the Blood Bank: A Multi-Omics Approach towards Identification of Causes and Consequences.

Joames K Freitas Leal,Vikram Sharma,Sara Rinalducci,Roland Brock,Edwin Lasonder,Giel Bosman,Giuseppina Fanelli,Jürgen Schiller

doi:10.3390/proteomes8020006

Abstract

Microvesicle generation is an integral part of the aging process of red blood cells in vivo and in vitro. Extensive vesiculation impairs function and survival of red blood cells after transfusion, and microvesicles contribute to transfusion reactions. The triggers and mechanisms of microvesicle generation are largely unknown. In this study, we combined morphological, immunochemical, proteomic, lipidomic, and metabolomic analyses to obtain an integrated understanding of the mechanisms underlying microvesicle generation during the storage of red blood cell concentrates. Our data indicate that changes in membrane organization, triggered by altered protein conformation, constitute the main mechanism of vesiculation, and precede changes in lipid organization. The resulting selective accumulation of membrane components in microvesicles is accompanied by the recruitment of plasma proteins involved in inflammation and coagulation. Our data may serve as a basis for further dissection of the fundamental mechanisms of red blood cell aging and vesiculation, for identifying the cause-effect relationship between blood bank storage and transfusion complications, and for assessing the role of microvesicles in pathologies affecting red blood cells.

Highlights

In the blood bank, red blood cells (RBCs) are exposed to various stressful circumstances that affect their structure and function
To identify aging-related changes in RBC derived vesicles, MVs were isolated from blood bank units after
We found a considerable increase in the concentration of RBC-derived MVs during storage from 4300 ± 1000

Summary

Introduction

In the blood bank, red blood cells (RBCs) are exposed to various stressful circumstances that affect their structure and function. There is an increase in removal signals on the RBC surface, caused by the generation of senescent cell antigens [8,9], the exposure of phosphatidylserine [10,11], and a decrease in concentration and/or activity of CD47 [12,13]. Associated—and possibly causative—processes are the accumulation of oxidized proteins and lipids, increased protein breakdown, depletion of ATP, alterations in ion concentrations, and disturbed phospholipid organization [14]. Proteomes 2020, 8, 6 by the formation of microvesicles [15,16], making microvesicle generation an important consequence of RBC aging in vitro.

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Conclusion