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Early studies considered that fibrinogen receptor (glycoprotein [GP] IIb–IIIa or platelet integrin α IIb β 3 ) is the binding site for low-density lipoprotein (LDL) and high-density lipoprotein type 3 (HDL 3 ). Recent data, however, do not support the hypothesis that the binding of LDL to human intact resting platelets is related to integrin α IIb β 3 . In this study we present evidence that platelet integrin α IIb β 3 is also not involved in the interaction of HDL 3 and human intact resting platelets. Firstly, specific ligands for platelet integrin α IIb β 3 , such as fibrinogen, vitronectin, von Willebrand factor and fibronectin, were unable to inhibit the binding of HDL 3 to intact resting platelets. Secondly, the HDL 3 binding characteristics ( K d and B max values), the activation of protein kinase C (PKC) and the inhibition of thrombin-induced inositoltriphosphate (IP 3 ) formation and calcium (Ca 2+ ) mobilization mediated by HDL 3 particles were similar in platelets from control subjects and patients with type I and type II Glanzmann's thrombasthenia, which are characterized by total and partial lack of GPIIb–IIIa and fibrinogen, respectively. In contrast, nitrosylation of tyrosine residues of HDL 3 by tetranitromethane fully abolished both the ability of particles to interact with its specific binding sites and the functional effects. Thirdly, polyclonal antibodies against the GPIIb–IIIa complex (edu-3 and 5B12), human antiserums against platelet alloantigens (anti-Bak a/B and anti-PL A1/2 ), anti-integrin subunits (anti-α V and anti-β 3 ), and a wide panel of monoclonal antibodies (mAbs) against well-known epitopes of GPIIb (M3, M4, M5, M6, M8 and M95-2b) and GPIIIa (P23-7, P33, P37, P40, and P97) did not affect the binding of HDL 3 particles to human intact resting platelets. Overall results show that neither the GPIIb–IIIa complex nor GPIIb or GPIIIa individually are the membrane binding proteins for HDL 3 on intact resting platelets. |
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