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Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors
Open accessAbstract
Previous studies have shown that during the lifespan of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. To study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by Na2(51) CrO4. Such labeled vesicles were injected into recipient rats. Within 5 minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes, Kupffer cells contained considerable amounts of hemoglobin and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by preinjection of the scavenger-receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in humans.
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“Once in the liver, the monocytes upregulate scavenger receptors for the uptake of damaged RBC (dRBC) and induced HO1 and FPN1 expression for heme breakdown and subsequent iron export (Willekens et al., 2005).”
From Iron in infection and immunity (2020) · cites this paper as Willekens et al., 2005
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Metadata
- Authors
- Willekens, F. L. A., Werre, J. M., Kruijt, J. K., Roerdinkholder-Stoelwinder, B., Groenen-Döpp, Y. A. M., van den Bos, A. G., Bosman, G. J. C. G. M., & van Berkel, T. J. C.
- Affiliations
- Leiden University (NL)
- From the Department of Clinical Chemistry, Rijnstate Hospital, Arnhem; Department of Blood Transfusion and Transplantation Immunology and Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen; and Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-01
- Volume
- 105
- Issue
- 5
- Pages
- 2141-2145
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2113060990
- Cited by
- 280
- References
- 14
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 10 · 2023: 19 · 2022: 17 · 2021: 14 · 2020: 18 · 2019: 16 · 2018: 9 · 2017: 20 · 2016: 16 · 2015: 16 · 2014: 18 · 2013: 16 · 2012: 12
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- Kupffer cells, scavenger receptors, hepatic uptake, polyinosinic acid, phosphatidylserine, erythrocyte clearance, hemolysis
- MeSH terms
- Animals, Erythrocyte Aging, Erythrocytes, Hemoglobins, Kinetics, Kupffer Cells, Liposomes, Liver Circulation, Male, Receptors, Immunologic, Tissue Distribution, Rats, Wistar, Cytoplasmic Vesicles, Receptors, Scavenger, Rats
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