INTERLEUKIN-1-ALPHA IN BLOOD HAS DIRECT ACCESS TO CORTICAL BRAIN-CELLS
INTERLEUKIN-1-ALPHA IN BLOOD HAS DIRECT ACCESS TO CORTICAL BRAIN-CELLS
复制标题
DOI：
10.1016/0304-3940(93)90224-9
复制
发表时间：
1993-11-26
影响因子：
2.5
通讯作者：
GUTIERREZ, EG
中科院分区：
文献类型：
--
作者：
BANKS, WA;KASTIN, AJ;GUTIERREZ, EG
白细胞介素-1 α (IL-1 α) 是一种由外周免疫系统分泌的免疫调节蛋白，影响中枢神经系统 (CNS)。 IL-1α可以以完整的形式直接进入大脑实质以改变痘印功能，或者它可以被包含血脑屏障（BBB）的毛细血管床阻断或隔离，该毛细血管床通常会阻碍循环蛋白质进入大脑和脑脊液（CSF）。我们在这里展示了通过使用选择性白细胞介素受体拮抗剂（IL-1ra）、毛细血管耗竭法、高效液相色谱（HPLC）和未标记的IL-1α饱和，静脉内注射的放射性标记的IL-1α直接以完整形式进入CNS。这种情况也发生在大脑皮层（没有室周器官（CVO）的区域）和脑脊液（没有毛细血管的区域）中。毛细血管还可以以可饱和的方式隔离IL-1α，表明它们可能是载体介导的IL-1α进入CNS的位点。因此，结果表明，循环中的 IL-1 α 可通过可饱和转运系统直接进入 BBB 后面的皮质脑细胞，该系统提供了大脑和免疫系统相互作用的主要途径。
Interleukin-1 alpha(IL-1 alpha), an immunoregulatory protein secreted by the peripheral immune system, affects the central nervous system (CNS). IL-1 alpha could directly enter the parenchyma of the brain in intact form to alter blain function, or it could be blocked or sequestered by the capillary bed comprising the blood-brain barrier (BBB) that normally retards entry of circulating proteins to the brain and cerebrospinal fluid (CSF). We show here by use of the selective interleukin receptor antagonist (IL-1ra), capillary depletion method, high performance liquid chromatography (HPLC) and saturation with unlabeled IL-1 alpha that radioactively labeled IL-1 alpha injected iv directly enters the CNS in intact form. This also occurs in the brain cortex, an area devoid of circumventricular organs (CVOs), and in the CSF, an area devoid of capillaries. Capillaries can also sequester IL-1 alpha in a saturable manner, suggesting that they may be the site for the carrier-mediated entry of IL-1 alpha into the CNS. Thus, the results show that circulating IL-1 alpha has direct access to cortical brain cells behind the BBB through a saturable transport system that provides a major pathway by which the brain and immune system interact.