Characterisation of species differences in the platelet ADP and thrombin response.
ABSTRACT A number of animal models are used to study platelet-dependent diseases. In the present investigation, we have used a simple flow cytometry assay to evaluate platelet function in man, rat, mouse, guinea pig and dog.
Platelet activation was evaluated in diluted whole blood by measuring fibrinogen binding to activated platelets using a polyclonal anti-human fibrinogen antibody that cross-reacts with fibrinogen from all species tested. The assay was used to evaluate platelet function with respect to ADP and thrombin sensitivity. The relative importance of the two platelet ADP receptors and total ADP in the thrombin response was also studied by using receptor-specific antagonists and apyrase, respectively.
Mouse platelets were most sensitive to both agonists. Unlike in man and dog the maximal response to ADP was greater than to thrombin in mouse, rat and guinea pig. P2Y(12) blockade was in all species equally effective as ADP removal in inhibiting thrombin-induced platelet activation whereas P2Y(1) blockade was almost ineffective.
The present study describes a simple platelet function test that can be used to evaluate platelet function in man, rat, mouse, guinea pig and dog. Platelets from the tested species differed in their sensitivity to ADP and thrombin. In contrast to human and canine platelets, mouse, rat and guinea pig platelets displayed a stronger maximal response to ADP than to thrombin. In terms of the relative contribution of P2Y(1) and P2Y(12) in the thrombin response, the P2Y(12) receptor was the key receptor in all species and its blockade gave equal effect as total removal of ADP.
Article: Platelet signaling-A primer[Show abstract] [Hide abstract]
ABSTRACT: To review the receptors and signal transduction pathways involved in platelet plug formation and to highlight links between platelets, leukocytes, endothelium, and the coagulation system. Original studies, review articles, and book chapters in the human and veterinary medical fields. Platelets express numerous surface receptors. Critical among these are glycoprotein VI, the glycoprotein Ib-IX-V complex, integrin α(IIb) β(3) , and the G-protein-coupled receptors for thrombin, ADP, and thromboxane. Activation of these receptors leads to various important functional events, in particular activation of the principal adhesion receptor α(IIb) β(3) . Integrin activation allows binding of ligands such as fibrinogen, mediating platelet-platelet interaction in the process of aggregation. Signals activated by these receptors also couple to 3 other important functional events, secretion of granule contents, change in cell shape through cytoskeletal rearrangement, and procoagulant membrane expression. These processes generate a stable thrombus to limit blood loss and promote restoration of endothelial integrity. Improvements in our understanding of how platelets operate through their signaling networks are critical for diagnosis of unusual primary hemostatic disorders and for rational antithrombotic drug design.02/2012; 22(1):5-29. DOI:10.1111/j.1476-4431.2011.00704.x
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ABSTRACT: IntroductionPericardial effusion is a clinical condition requiring multidisciplinary management. There are several surgical techniques for its diagnosis and treatment. In the present study we report our experience in performing a pericardial window (PW) by videothorascopy.Cirugía Española 12/2011; DOI:10.1016/j.ciresp.2011.05.006 · 0.89 Impact Factor