Cited by 280Phagocytosis and Immune RegulationErythrocyte Function and PathophysiologyHemoglobin structure and function

Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors

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Willekens, Frans L. A., Werre, Jan M., Kruijt, J. Kar, Roerdinkholder-Stoelwinder, Bregt, Groenen-Döpp, Yvonne A. M., van den Bos, Annegeet G., Bosman, Giel J. C. G. M., van Berkel, Theo J. C.·2005·Blood

Abstract

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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Crossref · 10.1182/blood-2004-04-1578

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  • Once in the liver, monocytes upregulate scavenger receptors for uptake of damaged RBC and induce HO1 and FPN1 expression for heme breakdown and subsequent iron export.

    “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

    The Abstract and Discussion report that liver Kupffer cells remove RBC-derived vesicles through scavenger receptors. They do not show that arriving monocytes upregulate those receptors or take up whole damaged RBCs, and they do not report HO1 or FPN1 induction, heme breakdown, or iron export. The indexed passages provide section labels but no page numbers. (LLM, conf=0.87)

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Research works printed but not linked: 1

  1. Baker JRJ, Bullock GR, Crawford N, et al. Local- ization in platelets of sodium 51 Cr-chromate, 125 I- antibody to whole membrane, and 3 H-diisopropy- lfluorophosphate using electron microscopic autoradiography. Am J Pathol. 1977;88:277-290.

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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
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
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 › Erythrocyte Function and Pathophysiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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