Zatta A, Zanetti A, Dejana E, Prosdocimi M
Fidia Research Laboratories, Abano Terme, Italy.
Agents Actions. 1987 Oct;22(1-2):151-8. doi: 10.1007/BF01968831.
The aim of this study was to investigate the mechanism involved in beta-thromboglobulin (BTG) release induced by platelet activating factor (PAF) in human platelet-rich plasma (PRP) and washed platelets (WP) during aggregation. PAF was used in PRP at increasing concentrations starting at its threshold concentration for irreversible aggregation (TAC: 90-150 nM). In citrated PRP, PAF induced release of BTG (80-95% of total content) and thromboxane B2 (TXB2) formation (30-40 pmol/ml). At low PAF concentrations aggregation and BTG release were blocked by apyrase (a scavenger of ADP), by ASA (an inhibitor of cyclooxygenase) and by BM 13177 (a thromboxane receptor antagonist). Higher concentrations of PAF overcame the effect of apyrase, but only induced reversible aggregation and minor release in the presence of ASA or BM 13177. In heparinized PRP, PAF induced full irreversible aggregation, but only very low BTG release (about 25% of total content) and thromboxane synthesis (2-3 pmol/ml). WP resuspended in the presence of 2 mmol/l Ca2+ seldom responded to PAF alone, as previously shown by others, but full aggregation could be induced by concomitant addition of subthreshold concentrations of PAF (25-50 nM) and epinephrine (1 microM). In these conditions average BTG release from WP was less than 20% of the amount releasable by thrombin. In contrast, when WP were resuspended in the absence of Ca2+, stimulation by PAF + EPI induced sustained BTG release (40-50% of total content) and TXB2 synthesis (15-20 pmol/ml). We conclude that at low Ca2+ concentration PAF induces BTG release mainly through thromboxane-endoperoxides formation. In contrast, when [Ca2+] is normal, PAF does not or weakly induces thromboxane formation and BTG release.
本研究的目的是探讨在人富血小板血浆（PRP）和洗涤血小板（WP）聚集过程中，血小板活化因子（PAF）诱导β-血小板球蛋白（BTG）释放所涉及的机制。在PRP中使用PAF，起始浓度为其不可逆聚集的阈值浓度（TAC：90 - 150 nM），并逐渐增加浓度。在枸橼酸化PRP中，PAF诱导BTG释放（占总含量的80 - 95%）和血栓素B2（TXB2）生成（30 - 40 pmol/ml）。在低PAF浓度下，聚集和BTG释放被腺苷三磷酸双磷酸酶（一种ADP清除剂）、阿司匹林（一种环氧化酶抑制剂）和BM 13177（一种血栓素受体拮抗剂）所阻断。较高浓度的PAF克服了腺苷三磷酸双磷酸酶的作用，但在存在阿司匹林或BM 13177的情况下仅诱导可逆聚集和少量释放。在肝素化PRP中，PAF诱导完全不可逆聚集，但仅诱导非常低的BTG释放（约占总含量的25%）和血栓素合成（2 - 3 pmol/ml）。如其他人先前所示，在2 mmol/l Ca2+存在下重悬的WP很少单独对PAF产生反应，但通过同时添加亚阈值浓度的PAF（25 - 50 nM）和肾上腺素（1 microM）可诱导完全聚集。在这些条件下，WP的平均BTG释放量低于凝血酶可释放量的20%。相反，当WP在无Ca2+的情况下重悬时，PAF + EPI刺激诱导持续的BTG释放（占总含量的40 - 50%）和TXB2合成（15 - 20 pmol/ml）。我们得出结论，在低Ca2+浓度下，PAF主要通过血栓素 - 内过氧化物的形成诱导BTG释放。相反，当[Ca2+]正常时，PAF不诱导或微弱地诱导血栓素形成和BTG释放。
