Low density lipoprotein-induced growth of U937 cells: a novel method to determine the receptor binding of low density lipoprotein.
U937 is a monocytic cell-line originally derived from a histiocytic lymphoma. In serum-free medium the growth of U937 cells was stimulated by addition of low density lipoprotein (LDL). Methylation of LDL impaired its ability to be taken up in U937 cells as well as the capacity to stimulate the growth of these cells. Pretreatment of U937 cells with a monoclonal antibody against the LDL receptor was also found to completely block the growth-promoting effect of LDL. Exposure of U937 cells to liposomes with a lipid composition similar to that of LDL did not stimulate the growth rate. These findings demonstrate that growth of U937 cells under serum-free conditions is related to the amount of LDL ingested by the cells and that this uptake is mediated by binding of LDL to the LDL receptor. To determine if LDL-induced growth of U937 cells can be used to identify LDL with decreased binding to the LDL receptor, U937 cells were incubated with LDL isolated from a patient with familial defective apolipoprotein B-100 and from subjects with various lipoprotein phenotypes. LDL containing defective apolipoprotein B-100 was found to be less than half as effective as LDL from normolipidemic controls in stimulating growth of U937 cells. LDL isolated from patients with hyperlipoproteinemia type IIa and IV did not differ from normal LDL in their ability to promote growth of U937 cells. The present results suggest that LDL-induced growth of U937 cells may be used as an assay to identify defective receptor binding of LDL.
Frostegård
J
J
Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Hamsten
A
A
Gidlund
M
M
Nilsson
J
J
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000209:etiology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D003470:Culture Media; D008077:Lipoproteins, LDL; D008081:Liposomes; D011973:Receptors, LDL