Zhou W, Javors M A, Olson M S
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
J Immunol. 1992 Sep 1;149(5):1763-9.
The role of platelet-activating factor (PAF) in heterotypic cell to cell interactions in a rabbit neutrophil-platelet mixture model was investigated. Platelets were exposed to each of three chemotactic agonists: PAF, leukotriene B4 (LTB4), or FMLP. Only PAF stimulated aggregation, [3H]serotonin secretion, and cytosolic Ca2+ mobilization in platelets alone. However, platelets were stimulated by LTB4 and FMLP in the presence of neutrophils. This neutrophil-dependent platelet activation was blocked by pretreatment of platelets with PAF receptor antagonists, and was prevented by desensitization of platelets to PAF. Furthermore, the time-course of platelet activation showed a positive correlation with PAF production by neutrophils stimulated with either LTB4 or FMLP. The PAF-mediated neutrophil-platelet interaction was dependent on direct cell to cell contact, as demonstrated by experiments in which the majority of newly formed PAF was neutrophil associated (rather than released). Platelet activation did not occur when the neutrophil-platelet mixture was not stirred, minimizing cell to cell contact, or when platelets were challenged with a cell-free supernatant prepared from neutrophils activated with LTB4 or FMLP. Finally, the neutrophil-platelet interaction was abolished by SC-49992, a peptidomimetic of the fibrinogen binding sequence Arg-Gly-Asp-Phe, indicating a Arg-Gly-Asp-specific recognition mechanism. Our results demonstrate that neutrophil-generated PAF plays a crucial role in neutrophil-dependent platelet activation in this model system. This type of intercellular signaling event may be important in certain inflammatory or thrombotic processes.
研究了血小板活化因子（PAF）在兔中性粒细胞 - 血小板混合模型中异型细胞间相互作用中的作用。将血小板分别暴露于三种趋化激动剂：PAF、白三烯B4（LTB4）或N - 甲酰甲硫氨酸 - 亮氨酸 - 苯丙氨酸（FMLP）。仅PAF能单独刺激血小板聚集、[3H]5 - 羟色胺分泌和胞质Ca2 +动员。然而，在中性粒细胞存在的情况下，LTB4和FMLP能刺激血小板。这种中性粒细胞依赖性血小板活化可被用PAF受体拮抗剂预处理血小板所阻断，并且可通过使血小板对PAF脱敏来预防。此外，血小板活化的时间进程与用LTB4或FMLP刺激的中性粒细胞产生PAF呈正相关。PAF介导的中性粒细胞 - 血小板相互作用依赖于细胞间的直接接触，这通过实验得以证明，在这些实验中，大多数新形成的PAF与中性粒细胞相关（而非释放）。当中性粒细胞 - 血小板混合物未搅拌以尽量减少细胞间接触时，或者当用由LTB4或FMLP激活的中性粒细胞制备的无细胞上清液刺激血小板时，血小板活化不会发生。最后，中性粒细胞 - 血小板相互作用被SC - 49992（一种纤维蛋白原结合序列Arg - Gly - Asp - Phe的肽模拟物）消除，表明存在Arg - Gly - Asp特异性识别机制。我们的结果表明，在该模型系统中，中性粒细胞产生的PAF在中性粒细胞依赖性血小板活化中起关键作用。这种细胞间信号传导事件在某些炎症或血栓形成过程中可能很重要。
