LDL binding sites on platelets differ from the "classical" receptor of nucleated cells.

Abstract

Washed human platelets bound radioiodinated low density lipoprotein ( 125 I-LDL) to a class of saturable binding sites; they numbered 1,348±126 per platelet, and the dissociation constant (K D ) was 50.7±9 nM. I25I-LDL binding to platelets was reversible, and apparent equilibrium was attained within 25 minutes at 22°C and was characterized by forward and reverse rate constants of 1.47xlO4 Xsec"'xM" 1 and 8xlO~4xsec~' xM" 1 , respectively. Such binding was largely unaltered by temperature, divalent ions, and chelating agents. In addition, neither did receptor regulation (up or down) occur when platelets were loaded with cholesterol, nor did prostaglandin E, (PGE,) increase the binding of 12S I-LDL to platelets. On the other hand, the specificity of LDL binding was not typical of the LDL receptor of nucleated cells. Lipoproteins competed for the occupancy of LDL binding sites in platelets with the following order of potency: very low density >> intermediate density > high density subfraction 2. High density lipoprotein subfraction 3, heparin, and PGE, had no effect on this binding.

Hepatitis C virus interacts with human platelet glycoprotein VI

“…Platelets do not express CD81 (Levy et al, 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al, 2004;Pedreno et al, 1992), which are putative HCV receptors (Agnello et al, 1999;Gardner et al, 2003;Lozach et al, 2003; Monazahian et al, 1999;Pileri et al, 1998;Pohlmann et al, 2003;Scarselli et al, 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.…”

“…Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al, 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al, 1998(Lee et al, , 1993Olinger et al, 2000), echovirus 1 (Xing et al, 2004), hantavirus (Gavrilovskaya et al, 1998) and the flavivirus dengue type 2 (Wang et al, 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al, 2004), suggesting a direct viral effect on platelet count.Platelets do not express CD81 (Levy et al, 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al, 2004;Pedreno et al, 1992), which are putative HCV receptors (Agnello et al, 1999;Gardner et al, 2003;Lozach et al, 2003; Monazahian et al, 1999;Pileri et al, 1998;Pohlmann et al, 2003;Scarselli et al, 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.…”

Binding of Low Density Lipoprotein to Platelet Apolipoprotein E Receptor 2′ Results in Phosphorylation of p38MAPK

“…The finding that the signaling pathway is initiated by the apoB100 component of LDL may point to the involvement of an LDL-binding receptor. However, platelets are known to lack the classical LDL-R as well as LDL receptorrelated protein-1 (LRP1) (12,13). Recently, a splice variant of apolipoprotein E receptor-2 (apoER2) has been identified in platelets and megakaryocytic cell lines (14).…”

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α IIb β 3 –Mediated Signaling

“…[1][2][3][4][5] In subjects deficient in apolipoprotein (apo) B or E receptor, LDL binding to platelets is preserved, indicating that another binding site must be involved. 3 Platelet aggregation is mediated via fibrinogen binding to sites on the integrin-␣ IIb ␤ 3 complex that become exposed once the cell is activated. The same complex has been implicated in the binding of LDL because the separate subunits bound 125 I-LDL on Western blots.…”