Total and selective desensitisation of human platelets to synthetic platelet activating factor (PAF): evidence that extracellular PAF does not mediate collagen-induced aggregation |
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Authors: | B Nunn |
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Affiliation: | Beecham Pharmaceuticals Research Division, Biosciences Research Centre, Great Burgh, Yew Tree Bottom Road, Epsom, Surrey, KT18 5XQ England |
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Abstract: | A technique is described that renders human platelets totally insensitive to synthetic PAF. The procedure involves gently mixing human citrated platelet-rich plasma (PRP) with 0.1 microM PAF at room temperature. After 3-5 min, a further addition of 0.1 microM PAF is made, followed 3-5 min later by 1 microM PAF. Preparations so treated did not aggregate in response to 50 microM PAF whereas control PRP always responded to 0.05 microM PAF. The selectivity of the desensitisation procedure depended on the presence of aspirin. In the absence of aspirin, collagen-induced aggregation was slightly inhibited, but so too was primary aggregation in response to ADP and the thromboxane receptor agonist, U46619. When PRP was pretreated with aspirin to prevent any secondary aggregation during the desensitisation procedure, collagen-induced aggregation and primary aggregation in response to ADP were essentially unchanged by total desensitisation to PAF. It is concluded that endogenous PAF acting extracellularly does not mediate or help to mediate collagen-induced aggregation in human citrated PRP. |
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Keywords: | Platelet activating factor Desensitisation Collagen Aggregation Mechanisms |
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