Journal of Lipid Research, Vol 25, 888-902, Copyright © 1984 by Lipid Research, Inc.
Pigeon aortic smooth muscle cells lack a functional low density lipoprotein receptor pathway
RK Randolph and RW St. Clair
The low density lipoprotein (LDL) receptor pathway was studied in aortic
smooth muscle cells from atherosclerosis-susceptible White Carneau pigeons
and compared with rhesus monkey cells whose LDL receptor pathway has been
previously characterized. Pigeon LDL was bound with high affinity in a
saturable manner to both pigeon and monkey aortic smooth muscle cells. The
kinetics of binding were different, however. LDL binding to pigeon cells
exhibited positive cooperativity at low LDL concentrations and at least two
classes of binding sites. The same pigeon LDL bound to monkey cells in a
manner consistent with a single class of binding sites. Thus, these
differences were a property of the pigeon cells and not the result of
differences in the LDL. On the average, pigeon cells bound less than 50%
the amount of LDL as monkey cells. Despite the surface binding to pigeon
cells, little of the LDL was internalized, whereas pigeon LDL was actively
internalized by monkey cells. Consistent with this observation, chloroquine
and leupeptin had no effect on accumulation of LDL or on LDL degradation by
pigeon cells, and incubation of pigeon cells with LDL produced no increase
in cellular cholesteryl ester content. Binding of LDL to pigeon cells also
differed from that of monkey cells by being unaffected by pretreatment with
the proteolytic enzyme pronase, and by not requiring calcium. Binding was
not specific for LDL since acetyl-LDL, and to a lesser degree HDL, were
able to compete for LDL binding. Incubation with lipoprotein-deficient
serum decreased LDL binding in pigeon cells while 25-OH cholesterol caused
an increase in binding; both effects are opposite of that seen with the
same LDL in mammalian cells. Preincubation with LDL or cholesterol
dissolved in ethanol were without effect on LDL binding in pigeon cells,
even though they produced significant increases in cellular free
cholesterol content. In spite of the failure to internalize LDL, there was
considerable degradation of LDL. This apparently occurred on the cell
surface rather than by internalization and degradation within the lysosomes
as occurs in mammalian cells. The functional significance of LDL binding to
pigeon smooth muscle cells is unclear. The characteristics of binding
resemble that of a nonspecific lipoprotein receptor referred to by others
as the "lipoprotein receptor" or the "EDTA-insensitive receptor." It is
apparent, however, that White Carneau pigeon aortic smooth muscle cells
lack a functional LDL receptor pathway and in this way resemble cells from
human beings with homozygous familial hypercholesterolemia or from Watanabe
rabbits.
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