Platelet integrin alpha IIb beta 3 (GPIIb-IIIa) is not implicated in the binding of LDL to intact resting platelets
| Autor: | Rosa Fernández, Miguel Angel Elorza, C Cullaré, Javier Pedreño, Antonia Barceló, Conxita de Castellarnau |
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| Rok vydání: | 1997 |
| Předmět: |
Blood Platelets
Binding Sites biology Chemistry Fibrinogen receptor Binding protein Lipoprotein(a) Platelet Glycoprotein GPIIb-IIIa Complex Molecular biology Lipoproteins LDL Radioligand Assay Thrombasthenia Biochemistry biology.protein Humans Platelet Integrin Alpha-IIb/Beta-3 Cardiology and Cardiovascular Medicine Lipoprotein |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 17(1) |
| ISSN: | 1079-5642 |
| Popis: | It has been suggested that the fibrinogen receptor (glycoprotein [GP] IIb-IIIa or platelet integrin α IIb β 3 ) could be the binding site for low-density lipoprotein (LDL); however, recent data do not support this. Furthermore, GPIIb and not the GPIIb-IIIa complex is the main binding protein for lipoprotein(a) [Lp(a)]. In the present study, we have investigated the interaction between Lp(a) particles and platelet LDL binding sites and whether platelet integrin α IIb β 3 is implicated. Displacement experiments showed that 125 I-LDL binding to intact resting platelets was inhibited with the same apparent affinity by both unlabeled LDL and apolipoprotein(a)-free lipoprotein particles [Lp(a) − , an LDL-like particle prepared from Lp(a)]. Hill coefficients for displacement curves suggested that a single set of binding sites was involved. In contrast, both native and oxidized Lp(a) particles were unable to inhibit platelet LDL binding. Furthermore, platelets bound 125 I-Lp(a) − particles to a class of saturable binding sites numbering approximately 1958±235 binding sites per platelet with a dissociation constant ( K d ) of 48.3±12×10 −9 mol/L. These values were similar to those obtained for LDL. In contrast to Lp(a), evidence indicates that platelet integrin α IIb β 3 was not involved in the interaction of LDL and intact resting platelets. First, specific ligands for platelet integrin α IIb β 3 , such as fibrinogen, vitronectin, and fibronectin, were unable to inhibit the binding of LDL to intact resting platelets. Second, similar LDL binding characteristics ( K d and B max values) were found in platelets from control subjects and patients with type I and type II Glanzmann's thrombasthenia, characterized by total and partial lack of GPIIb-IIIa and fibrinogen, respectively. Third, 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, and M95-2b) and GPIIIa (P23-7, P33, P37, P40, and P97) did not affect platelet LDL binding. Finally, in contrast to the proaggregatory effect of native and oxidized LDL, both native and oxidized Lp(a) particles caused a significant dose-dependent decrease of collagen-induced platelet aggregation. In conclusion, we demonstrate that neither the GPIIb-IIIa complex nor GPIIb and GPIIIa individually are membrane binding proteins for LDL on intact resting platelets. Lp(a) particles do not interact with platelet LDL binding sites, and their biological response is clearly different from that of LDL. |
| Databáze: | OpenAIRE |
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