| First Author | Holm TM | Year | 2002 |
| Journal | Blood | Volume | 99 |
| Issue | 5 | Pages | 1817-24 |
| PubMed ID | 11861300 | Mgi Jnum | J:75090 |
| Mgi Id | MGI:2175936 | Doi | 10.1182/blood.v99.5.1817 |
| Citation | Holm TM, et al. (2002) Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI. Blood 99(5):1817-24 |
| abstractText | 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. |
