Ohnishi T, Hayakawa T, Shapiro W R
Department of Neurosurgery, Osaka University Medical School, Japan.
Acta Neurochir Suppl (Wien). 1990;51:137-9. doi: 10.1007/978-3-7091-9115-6_46.
The effect of conditioned media obtained from two human malignant gliomas and normal human glia on rat brain capillary permeability was investigated by measuring the entry of 14C-aminoisobutyric acid by a quantitative autoradiographic method. Conditioned media were concentrated 50-fold to create SUP-C. The SUP-C contained proteins with a molecular weight greater than 10 kD. The SUP-C from glioma cells markedly increased brain capillary permeability, whereas that from normal glial cells did not. The activity of capillary permeability factor in the SUP-C was significantly inhibited by pretreatment of animals with dexamethasone or BW755C (lipoxygenase inhibitor), but not with indomethacin. On the other hand, coincubation of glioma cells with dexamethasone produced SUP-C whose capillary permeability activity was about one and a half times greater than that without dexamethasone. These results indicate that human malignant glioma cells secrete a protein factor that increases brain capillary permeability. Glucocorticoids inhibit the effect of the factor by directly acting on capillary endothelial cells, possibly through the inhibition of phospholipase A2 activity, resulting in a decrease of lipoxygenase rather than cyclo-oxygenase products.
通过定量放射自显影法测量¹⁴C-氨基异丁酸的进入情况，研究了从两种人类恶性神经胶质瘤和正常人神经胶质细胞获得的条件培养基对大鼠脑毛细血管通透性的影响。将条件培养基浓缩50倍制成SUP-C。SUP-C含有分子量大于10 kD的蛋白质。来自胶质瘤细胞的SUP-C显著增加脑毛细血管通透性，而来自正常神经胶质细胞的SUP-C则无此作用。用地塞米松或BW755C（脂氧合酶抑制剂）预处理动物可显著抑制SUP-C中毛细血管通透因子的活性，但吲哚美辛则无此作用。另一方面，胶质瘤细胞与地塞米松共同孵育产生的SUP-C，其毛细血管通透活性比未用地塞米松时大约高1.5倍。这些结果表明，人类恶性神经胶质瘤细胞分泌一种增加脑毛细血管通透性的蛋白质因子。糖皮质激素可能通过抑制磷脂酶A2活性直接作用于毛细血管内皮细胞，从而抑制该因子的作用，导致脂氧合酶而非环氧化酶产物减少。
