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In vitro phagocytosis of liquid-stored red blood cells requires serum and can be inhibited with fucoidan and dextran sulphate
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.ORCID iD: 0000-0002-4341-1745
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.ORCID iD: 0000-0001-7157-3250
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
2020 (English)In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND AND OBJECTIVES: Red-blood-cells (RBCs) undergo structural and metabolic changes with prolonged storage, which ultimately may decrease their survival after transfusion. Although the storage-induced damage to RBCs has been rather well described biochemically, little is known about the mechanisms underlying the recognition and rapid clearance of the damaged cells by macrophages.

MATERIALS AND METHODS: We, here, used a murine model for cold (+4°C) RBC storage and transfusion. Phagocytosis of human or murine RBCs, liquid stored for 6-8 weeks or 10-14 days, respectively, was investigated in murine peritoneal macrophages.

RESULTS: The effects of storage on murine RBCs resembled that described for stored human RBCs with regard to decreased adenosine triphosphate (ATP) levels, accumulation of microparticles (MPs) during storage, and RBC recovery kinetics after transfusion. Under serum-free conditions, phagocytosis of stored human or murine RBCs in vitro was reduced by 70-75%, as compared with that in the presence of heat-inactivated fetal calf serum (FCS). Human serum promoted phagocytosis of stored human RBCs similar to that seen with FCS. By adding fucoidan or dextran sulphate (blockers of scavenger receptors class A (SR-A)), phagocytosis of human or murine RBCs was reduced by more than 90%. Phagocytosis of stored human RBCs was also sensitive to inhibition by the phosphatidylinositol 3 kinase-inhibitor LY294002, the ERK1/2-inhibitor PD98059, or the p38 MAPK-inhibitor SB203580.

CONCLUSION: RBCs damaged during liquid storage may be recognized by macrophage SR-A and serum-dependent mechanisms. This species-independent recognition mechanism may help to further understand the rapid clearance of stored RBCs shortly after transfusion.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020.
Keywords [en]
blood processing, quality management, transfusion medicine (in general)
National Category
Hematology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-170612DOI: 10.1111/vox.12922ISI: 000529301800001PubMedID: 32350880OAI: oai:DiVA.org:umu-170612DiVA, id: diva2:1429603
Funder
Swedish Research Council, 2012-2702Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-05-27

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Hult, AndreasToss, FredrikMalm, Christer B.Oldenborg, Per-Arne
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