Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI.

Published

Journal Article

Mammalian erythrocytes undergo a unique maturation process in which they discard their nuclei and organelles and assume a flexible biconcave shape. We found that altered plasma lipoprotein metabolism can profoundly influence these events. Abnormal erythrocyte morphology was observed in hypercholesterolemic mice lacking the high-density lipoprotein receptor SR-BI. This was exacerbated by feeding mice a high-cholesterol diet or, more dramatically, by inactivating the apolipoprotein E gene. Erythrocytes from SR-BI(-/-)/apolipoprotein E(-/-) mice and SR-BI(-/-) mice that were fed cholesterol had markedly increased membrane cholesterol. Their morphology appeared immature, with macrocytosis, irregular shape, and large autophagolysosomes. Autophagolysosomes from SR-BI(-/-)/apolipoprotein E(-/-) erythrocytes were expelled when the erythrocytes were transfused into wild-type animals or incubated in vitro with normolipidemic serum or the cholesterol-sequestering agent methyl cyclodextrin. We propose that autophagocytosis and phagolysosome expulsion are essential steps in erythroid maturation and that expulsion is inhibited in the presence of markedly increased cellular cholesterol.

Full Text

Duke Authors

Cited Authors

  • Holm, TM; Braun, A; Trigatti, BL; Brugnara, C; Sakamoto, M; Krieger, M; Andrews, NC

Published Date

  • March 2002

Published In

Volume / Issue

  • 99 / 5

Start / End Page

  • 1817 - 1824

PubMed ID

  • 11861300

Pubmed Central ID

  • 11861300

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood.v99.5.1817

Language

  • eng