Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.
Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.
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DOI：
10.1172/jci117316
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发表时间：
1994-07
期刊：
影响因子：
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通讯作者：
J. B. Watson;S. B. Getzler;D. Mosher
中科院分区：
文献类型：
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作者：
J. B. Watson;S. B. Getzler;D. Mosher
碱性成纤维细胞生长因子（bFGF）已被证明可以刺激血管损伤后的细胞增殖。bFGF的促有丝分裂活性需要与高亲和力受体和细胞表面硫酸乙酰肝素蛋白聚糖相互作用。我们测试了血小板因子4（PF 4）和其他血小板肝素结合蛋白调节bFGF刺激的[3 H]胸苷掺入成纤维细胞的能力。凝血酶刺激的血小板的上清液中含有bFGF诱导的有丝分裂的抑制剂，这种活性共洗脱与PF 4凝胶过滤，肝素-琼脂糖，和离子交换色谱。纯化的血小板反应蛋白和β-血小板球蛋白不抑制bFGF的促有丝分裂活性。PF 4抑制5 pM bFGF的活性，50%抑制浓度为75 nM。纯化的PF 4还抑制3 T3成纤维细胞的[3 H]胸苷的基础掺入和细胞单层损伤后发生的[3 H]胸苷掺入增加。PF 4不影响血清的促有丝分裂活性。PF 4对bFGF活性的抑制作用可被外源性肝素或4-硫酸软骨素所克服，这表明PF 4与细胞表面糖胺聚糖的结合可抑制有丝分裂。这些结果表明，在血管损伤和血小板活化部位释放的PF 4的重要作用是控制由破裂细胞释放bFGF引起的细胞增殖。
Basic fibroblast growth factor (bFGF) has been shown to stimulate cell proliferation after vascular injury. The mitogenic activity of bFGF requires interactions with both a high affinity receptor and a cell-surface heparan sulfate proteoglycan. We tested the ability of platelet factor 4 (PF 4) and other platelet heparin-binding proteins to modulate bFGF-stimulated [3H]thymidine incorporation into fibroblasts. The supernatant of thrombin-stimulated platelets contained an inhibitor of bFGF-induced mitogenesis; this activity coeluted with PF 4 upon gel filtration, heparin-agarose, and ion-exchange chromatography. Purified thrombospondin and beta-thromboglobulin did not inhibit the mitogenic activity of bFGF. PF 4 inhibited the activity of 5 pM bFGF with 50% inhibitory concentration of 75 nM. Purified PF 4 also inhibited the basal incorporation of [3H]thymidine into 3T3 fibroblasts and the increased [3H]thymidine incorporation occurring after wounding of a cell monolayer. PF 4 did not affect the mitogenic activity of serum. Inhibition of bFGF activity by PF 4 could be overcome by exogenous heparin or chondroitin-4-sulfate, suggesting that inhibition of mitogenesis is caused by binding of PF 4 to cell-surface glycosaminoglycans. These results indicate that an important role of PF 4 released at sites of vascular injury and platelet activation is to control cellular proliferation caused by the release of bFGF from ruptured cells.