Detection of a Protein in Human Platelet Membranes which Binds Low-density Lipoproteins

Sensitisation of human blood platelets by plasma low-density lipoproteins (LDL) is thought to involve an initial interaction between LDL and the platelet surface membrane. When washed, fully responsive platelets were incubated with radio-iodinated LDL, two phases of binding were identified; one due to saturable sites, binding about 1965 ± 177 (mean ± SEM) LDL molecules per platelet, and the other of low affinity but high capacity. The saturable sites could be distinguished from the LDL receptors of nucleated cells by their presence in patients with homozygous familial hypercholesterolaemia, by their resistance to pronase digestion, by their reduced affinity for apolipoprotein E (apoE), and by the absence of a requirement for calcium ions. Binding of LDL by platelets was rapid and apparently mediated by recognition of positively charged arginine and lysine residues within the protein constituent (apoB) of LDL, findings previously reported as characteristics of LDL stimulation of platelet aggregation. Blotting of electrophoretically separated platelet membrane proteins with radio-iodinated LDL revealed a single component, presumably the saturable, high affinity binding site, whose apparent molecular weight of approx. 140 000 was lower than that of the classical LDL receptor. We conclude that occupation of (glyco)proteins on the platelet surface membrane by LDL molecules enhances platelet reactivity.