ISSN:
1619-7089
Keywords:
Low-density lipoprotein
;
Iodine-123 labelling
;
Indium-111 labelling
;
Peripheral mononuclear cells
;
Familial hypercholesterolaemia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The binding of radiolabelled lipoproteins, iodine-123-labelled low-density. lipoprotein (LDL) and indium-111-labelled LDL, to peripheral blood mononuclear cells (MNCs) was compared in normolipaemic subjects and in patients with heterozygous familial hypercholesterolaemia (FH). 123I-LDL and 111In-LDL binding to MNCs exhibited high-affinity, highly specific, time- and temperature-dependent binding reaching saturation at concentrations above 50 nM. The number of LDL binding sites (Bmax) was significantly (P〈0.01) lower in FH patients (P〈0.001; 123I-LDL: Bmax 279±44 ng protein/108MNCs; 111In-LDL: Bmax 309±43 ng protein/108MNCs) as compared with controls (123I-LDL: Bmax 2874±246 ng protein/108 MNCs; 111In-LDL: Bmax 3145±339 ng protein/108 MNCs). The corresponding dissociation constants (K d) were 16±8 nM for 123I-LDL and 12±6 nM for 123In-LDL in healthy volunteers (123In-LDL vs 111In-LDL, P〈0.05). In FH patients, the K d values were 20±8 nM for 123I-LDL and 16±6 nM for 123In-LDL (P〈0.05 vs controls for both 123I-LDL and 111In-LDL). 111In-LDL binding to MNCs was inhibited (IC50) by 30±8 nM in healthy controls and 38±12 nM in FH patients (P〈0.05). 123In-LDL binding to MNCs was inhibited (IC50) by 34±8 nM in healthy controls and 46±10 nM in FH patients (P〈0.05). Taken together, these results suggest a reduced number of LDL receptors expressed on MNCs from FH patients. We conclude that 111In-LDL and 123I-LDL are equally well suited as a probe of receptor-mediated binding and uptake of LDL.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00285585
