Pseudo type III (PT-III)
dyslipoproteinemia is characterized by a plasma accumulation of
triglyceride-rich
lipoproteins (TRL) and their remnants. It mimics type III, but its etiology can not be ascribed to a genetic
apo E defect. In order to determine whether PT-III is associated with a genetic
lipoprotein receptor abnormality, we have measured (in cultured fibroblasts from affected and nonaffected individuals) the in vitro activity of three
lipoprotein receptors which are implicated in the catabolism of TRL, namely the
low-density lipoprotein receptor (
LDL-R), the
lipoprotein receptor-related
protein (LRP) and the
lipolysis-stimulated receptor (LSR). Specific cell association and degradation of 125I-LDL by
LDL-R-upregulated PT-III fibroblasts was not significantly different from that of control cells (103 +/- 10% and 98 +/- 17% of controls; 20 microg/ml 125I-
LDL). Specific cell association and degradation of rabbit 125I-beta-VLDL was also not significantly different. LRP activity was assessed by measuring the ability of PT-III and control cells to bind three different LRP
ligands: activated
alpha2-macroglobulin (alpha2M-MA),
lactoferrin and
apo E-enriched rabbit
beta-VLDL. No significant differences were observed (24.0 +/- 2.1 vs. 23.4 +/- 5.7 fmol/mg for 5 nM of 125I-alpha2M-MA; 4.8 +/- 0.3 vs. 5.2 +/- 1.3 microg/mg for 20 microg/ml of 125I-
lactoferrin; 319.4 +/- 51.2 vs. 309.5 +/- 23.2 ng/mg for 5 microg/ml of 125I-
beta-VLDL, PT-III vs. control, respectively). LSR activity, as assessed by the cell association or degradation of 125I-LDL by fibroblasts in the presence of 0.5 mM
oleate and human
leptin, was also not different. No evidence was obtained for deficient cellular recognition of PT-III TRL (d < 1.006 g/ml) by normal human fibroblasts or mouse macrophages. These results suggest that PT-III
dyslipoproteinemia is not due to an accumulation in plasma of poorly recognized TRL, nor due to a genetic defect in
LDL-R, LRP or LSR.