title: HDL cholesterol levels are an important factor for determining the lifespan of erythrocytes.
abstract: OBJECTIVE
  Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also develop anemia, as evidenced by accumulation of reticulocytes in the circulation. The objective of the current study was to delineate the mechanism underlying development of anemia in the absence of SR-BI.
  
  
  METHODS
  Expression of important mediators of erythropoiesis, as well as key enzymes in the degradation of erythrocytes, were analyzed using real-time polymerase chain reaction in SR-BI wild-type and SR-BI knockout mice. In addition, in vivo studies were performed using biotinylated erythrocytes to determine erythrocyte survival.
  
  
  RESULTS
  mRNA expression of TAL-1, GATA-1, FOG-1, erythropoietin receptor, and ferrochelatase, important mediators of erythropoiesis, was increased in spleens of SR-BI-deficient mice. In addition, the relative amount of early Ter119(high)CD71(high) -expressing erythroblasts was increased in SR-BI-deficient spleens. Interestingly, also expression of hemeoxygenase 1 and biliverdin reductase, enzymes involved in the degradation of erythrocytes, was increased. Furthermore, an elevated amount of conjugated bilirubin, the breakdown product of hemoglobin, was found in bile. Using biotinylated erythrocytes, we show that survival of erythrocytes was decreased in SR-BI-deficient mice. Thus, the observed increased erythropoiesis in the SR-BI-deficient mice is most likely a direct response to the reduced erythrocyte lifespan. Finally, we show that increased HDL cholesterol levels due to SR-BI deficiency induce erythrocyte cholesterol:phospholipid ratios, resulting in decreased deformability and increased osmotic fragility, thereby providing an explanation for the observed reduced lifespan.
  
  
  CONCLUSIONS
  SR-BI is not only essential for HDL cholesterol homeostasis and atherosclerosis susceptibility, but also for maintaining normal erythrocyte lifespan.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands.
authors.forename: Illiana
authors.initials: I
authors.lastname: Meurs
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Eva J A
authors.initials: EJ
authors.lastname: van Wanrooij
authors.forename: Reeni B
authors.initials: RB
authors.lastname: Hildebrand
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Max R
authors.initials: MR
authors.lastname: Hardeman
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
mesh_terms: D000740:Anemia / Q000209:etiology; D000818:Animals; D002784:Cholesterol / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood* / Q000502:physiology; D004905:Erythrocyte Aging / Q000235:genetics*; D004907:Erythrocyte Deformability; D004920:Erythropoiesis / Q000235:genetics; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009996:Osmotic Fragility; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D010743:Phospholipids / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051122:Scavenger Receptors, Class B / Q000172:deficiency; D013154:Spleen / Q000737:chemistry
chemical_list: D008076:Cholesterol, HDL; D010743:Phospholipids; D012333:RNA, Messenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D051547:Heme Oxygenase-1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase