Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice
Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice
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DOI：
10.1038/sj.jcbfm.9600198
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发表时间：
2006-03-01
影响因子：
6.3
通讯作者：
Planas, AM
中科院分区：
文献类型：
--
作者：
Justicia, C;Martín, A;Planas, AM
脑缺血触发涉及白细胞向实质浸润的炎症过程。循环中的白细胞通过粘附分子粘附在血管壁上。在这里，我们定量的血管细胞粘附分子-1（VCAM-1）在大脑，心脏和肺的体内表达后6至48小时短暂大脑中动脉（MCA）闭塞大鼠，通过静脉注射示踪剂放射性标记的抗VCAM-1抗体。在体内注射抗体后，通过免疫组织化学验证VCAM-1的血管定位。血管细胞粘附分子-1在缺血区域的微血管系统中被强烈诱导（24 h时为4倍），并且在较小程度上，在对侧半球和远程器官心脏中，但不在肺中，这表明炎症过程传播超出损伤的大脑。我们在大鼠和小鼠MCA闭塞后静脉内注射阻断剂量的抗VCAM-1抗体或对照抗体。我们评估了大鼠的神经评分，以及大鼠在第2天和小鼠在第4天的梗死体积。抗VCAM-1在大鼠或小鼠中均不能防止缺血性损伤。血管细胞粘附分子-1阻断显著减少缺血大鼠脑中ED 1（标记单核细胞/巨噬细胞/反应性小胶质细胞）阳性细胞的数量。然而，它并没有减少浸润的中性粒细胞和淋巴细胞以及总白细胞（CD 45阳性）的数量，而是呈增加的趋势。结果显示短暂局灶性缺血后VCAM-1的血管上调，但阻断VCAM-1没有益处，表明这不是中风治疗的治疗策略。
Cerebral ischemia triggers an inflammatory process involving the infiltration of leukocytes to the parenchyma. Circulating leukocytes adhere to the vascular wall through adhesion molecules. Here we quantified the in vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in the brain, heart and lungs from 6 to 48 h after transient middle cerebral artery (MCA) occlusion in rats, by intravenous injection of a tracer radiolabelled anti-VCAM-1 antibody. The vascular localization of VCAM-1 was verified by immunohistochemistry after in vivo injection of the antibody. Vascular cell adhesion molecule-1 was strongly induced (4-fold at 24 h) in the microvasculature of the ischemic area, and, to a lesser extent, in the contralateral hemisphere and in a remote organ, the heart, but not in the lungs, indicating that the inflammatory process propagates beyond the injured brain. We injected intravenously either blocking doses of anti-VCAM-1 antibodies or control antibodies after MCA occlusion in rats and mice. We evaluated the neurological score in rats, and infarct volume at 2 days in rats and at 4 days in mice. Anti-VCAM-1 did not protect against ischemic damage either in rats or in mice. Vascular cell adhesion molecule-1 blockade significantly decreased the number of ED1 (labeling monocytes /macrophages/reactive microglia)-positive cells in the ischemic rat brain. However, it did not reduce the numbers of infiltrating neutrophils and lymphocytes, and total leukocytes (CD45 positive), which showed a trend to increase. The results show vascular upregulation of VCAM-1 after transient focal ischemia, but no benefits of blocking VCAM-1, suggesting that this is not a therapeutical strategy for stroke treatment.