Linder B L, Chernoff A, Kaplan K L, Goodman D S
Proc Natl Acad Sci U S A. 1979 Aug;76(8):4107-11. doi: 10.1073/pnas.76.8.4107.
Platelet alpha-granules contain a factor that stimulates the proliferation of arterial smooth muscle cells and may play a role in atherogenesis. We have studied the role of arachidonic acid in mediating the release of the platelet-derived growth factor (PDGF) from human platelets. PDGF was assayed by stimulating of [(3)H]thymidine incorporation into DNA of mouse 3T3 cells. Platelet aggregation and the release of platelet factor 4,beta-thromboglobulin, and serotonin were also studied. A biphasic response pattern was observed when gel-filtered platelets were incubated with arachidonate over the concentration range 0.01-0.4 mM. At low arachidonate levels (approximately 0.025-0.1 mM), specific concentration-dependent aggregation and release of PDGF and of the other components were observed. This effect was not seen with any of five other fatty acids tested and was suppressed by indomethacin (25 muM). At higher arachidonate concentrations (approximately 0.15-0.35 mM), a concentration-dependent turn-off of both aggregation and release occurred. At these concentrations the platelets remained functional, and no release of lactate dehydrogenase was observed. A similar biphasic pattern of arachidonate-induced aggregation and release was observed with platelet-rich plasma, over a similar range of arachidonate to albumin mole ratios. These studies demonstrate that PDGF and other alpha-granule constituents can be released from platelets specifically by arachidonate via an indomethacin-sensitive pathway, most probably involving the platelet cyclooxygenase and conversion of arachidonate to prostaglandin metabolities. The mechanisms responsible for the turn-off of the specific arachidonate-mediated responses at higher arachidonate concentrations remain to be defined.
血小板α-颗粒含有一种能刺激动脉平滑肌细胞增殖的因子，可能在动脉粥样硬化形成中起作用。我们研究了花生四烯酸在介导人血小板释放血小板衍生生长因子（PDGF）中的作用。通过刺激[³H]胸苷掺入小鼠3T3细胞的DNA来测定PDGF。还研究了血小板聚集以及血小板因子4、β-血小板球蛋白和5-羟色胺的释放。当将凝胶过滤的血小板与浓度范围为0.01 - 0.4 mM的花生四烯酸盐孵育时，观察到双相反应模式。在低花生四烯酸盐水平（约0.025 - 0.1 mM）时，观察到PDGF和其他成分有特定的浓度依赖性聚集和释放。在测试的其他五种脂肪酸中均未观察到这种效应，且该效应被吲哚美辛（25 μM）抑制。在较高的花生四烯酸盐浓度（约0.15 - 0.35 mM）时，聚集和释放均出现浓度依赖性的停止。在这些浓度下，血小板仍保持功能，且未观察到乳酸脱氢酶的释放。在类似的花生四烯酸盐与白蛋白摩尔比范围内，富含血小板血浆也观察到类似的花生四烯酸盐诱导的聚集和释放双相模式。这些研究表明，PDGF和其他α-颗粒成分可通过花生四烯酸盐经吲哚美辛敏感途径从血小板中特异性释放，最可能涉及血小板环氧化酶以及花生四烯酸盐向前列腺素代谢产物的转化。在较高花生四烯酸盐浓度下导致特定花生四烯酸盐介导反应停止的机制仍有待确定。
