title: Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors.
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.
authors.affiliation: Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Frans L A
authors.initials: FL
authors.lastname: Willekens
authors.forename: Jan M
authors.initials: JM
authors.lastname: Werre
authors.forename: J Kar
authors.initials: JK
authors.lastname: Kruijt
authors.forename: Bregt
authors.initials: B
authors.lastname: Roerdinkholder-Stoelwinder
authors.forename: Yvonne A M
authors.initials: YA
authors.lastname: Groenen-Döpp
authors.forename: Annegeet G
authors.initials: AG
authors.lastname: van den Bos
authors.forename: Giel J C G M
authors.initials: GJ
authors.lastname: Bosman
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
mesh_terms: D000818:Animals; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000648:ultrastructure*; D006454:Hemoglobins; D007700:Kinetics; D007728:Kupffer Cells / Q000502:physiology*; D008081:Liposomes / Q000493:pharmacokinetics / Q000494:pharmacology; D008102:Liver Circulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D014018:Tissue Distribution
chemical_list: D006454:Hemoglobins; D008081:Liposomes; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger