Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage

Background/Aims: During storage, units of human red blood cells (pRBCs) experience membrane destabilization and hemolysis which may cause harm to transfusion recipients. This study investigates whether inhibition of acid sphingomyelinase could stabilize erythrocyte membranes and prevent hemolysis du...

Full description

Bibliographic Details
Main Authors: Richard S. Hoehn, Peter L. Jernigan, Alex L. Chang, Michael J. Edwards, Charles C. Caldwell, Erich Gulbins, Timothy A. Pritts
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2016-06-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/445627
_version_ 1818986689939374080
author Richard S. Hoehn
Peter L. Jernigan
Alex L. Chang
Michael J. Edwards
Charles C. Caldwell
Erich Gulbins
Timothy A. Pritts
author_facet Richard S. Hoehn
Peter L. Jernigan
Alex L. Chang
Michael J. Edwards
Charles C. Caldwell
Erich Gulbins
Timothy A. Pritts
author_sort Richard S. Hoehn
collection DOAJ
description Background/Aims: During storage, units of human red blood cells (pRBCs) experience membrane destabilization and hemolysis which may cause harm to transfusion recipients. This study investigates whether inhibition of acid sphingomyelinase could stabilize erythrocyte membranes and prevent hemolysis during storage. Methods: Human and murine pRBCs were stored under standard blood banking conditions with and without the addition of amitriptyline, a known acid sphingomyelinase inhibitor. Hemoglobin was measured with an electronic hematology analyzer and flow cytometry was used to measure erythrocyte size, complexity, phosphatidylserine externalization, and band 3 protein expression. Results: Cell-free hemoglobin, a marker of hemolysis, increased during pRBC storage. Amitriptyline treatment decreased hemolysis in a dose-dependent manner. Standard pRBC storage led to loss of erythrocyte size and membrane complexity, increased phosphatidylserine externalization, and decreased band 3 protein integrity as determined by flow cytometry. Each of these changes was reduced by treatment with amitriptyline. Transfusion of amitriptyline-treated pRBCs resulted in decreased circulating free hemoglobin. Conclusion: Erythrocyte storage is associated with changes in cell size, complexity, membrane molecular composition, and increased hemolysis. Acid sphingomyelinase inhibition reduced these changes in a dose-dependent manner. Our data suggest a novel mechanism to attenuate the harmful effects after transfusion of aged blood products.
first_indexed 2024-12-20T18:54:48Z
format Article
id doaj.art-8cbd18c5cc6c4a41aaffb3d6ae24029a
institution Directory Open Access Journal
issn 1015-8987
1421-9778
language English
last_indexed 2024-12-20T18:54:48Z
publishDate 2016-06-01
publisher Cell Physiol Biochem Press GmbH & Co KG
record_format Article
series Cellular Physiology and Biochemistry
spelling doaj.art-8cbd18c5cc6c4a41aaffb3d6ae24029a2022-12-21T19:29:32ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-06-0139133134010.1159/000445627445627Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte StorageRichard S. HoehnPeter L. JerniganAlex L. ChangMichael J. EdwardsCharles C. CaldwellErich GulbinsTimothy A. PrittsBackground/Aims: During storage, units of human red blood cells (pRBCs) experience membrane destabilization and hemolysis which may cause harm to transfusion recipients. This study investigates whether inhibition of acid sphingomyelinase could stabilize erythrocyte membranes and prevent hemolysis during storage. Methods: Human and murine pRBCs were stored under standard blood banking conditions with and without the addition of amitriptyline, a known acid sphingomyelinase inhibitor. Hemoglobin was measured with an electronic hematology analyzer and flow cytometry was used to measure erythrocyte size, complexity, phosphatidylserine externalization, and band 3 protein expression. Results: Cell-free hemoglobin, a marker of hemolysis, increased during pRBC storage. Amitriptyline treatment decreased hemolysis in a dose-dependent manner. Standard pRBC storage led to loss of erythrocyte size and membrane complexity, increased phosphatidylserine externalization, and decreased band 3 protein integrity as determined by flow cytometry. Each of these changes was reduced by treatment with amitriptyline. Transfusion of amitriptyline-treated pRBCs resulted in decreased circulating free hemoglobin. Conclusion: Erythrocyte storage is associated with changes in cell size, complexity, membrane molecular composition, and increased hemolysis. Acid sphingomyelinase inhibition reduced these changes in a dose-dependent manner. Our data suggest a novel mechanism to attenuate the harmful effects after transfusion of aged blood products.http://www.karger.com/Article/FullText/445627SphingomyelinaseBlood bankingStorage lesionHemolysis
spellingShingle Richard S. Hoehn
Peter L. Jernigan
Alex L. Chang
Michael J. Edwards
Charles C. Caldwell
Erich Gulbins
Timothy A. Pritts
Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
Cellular Physiology and Biochemistry
Sphingomyelinase
Blood banking
Storage lesion
Hemolysis
title Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
title_full Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
title_fullStr Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
title_full_unstemmed Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
title_short Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage
title_sort acid sphingomyelinase inhibition prevents hemolysis during erythrocyte storage
topic Sphingomyelinase
Blood banking
Storage lesion
Hemolysis
url http://www.karger.com/Article/FullText/445627
work_keys_str_mv AT richardshoehn acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT peterljernigan acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT alexlchang acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT michaeljedwards acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT charlesccaldwell acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT erichgulbins acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage
AT timothyapritts acidsphingomyelinaseinhibitionpreventshemolysisduringerythrocytestorage