α4 integrin is a regulator of leukocyte recruitment after experimental intracerebral hemorrhage.
α4 integrin is a regulator of leukocyte recruitment after experimental intracerebral hemorrhage.
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DOI：
10.1161/strokeaha.114.005551
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发表时间：
2014-08
期刊：
影响因子：
8.3
通讯作者：
Sansing LH
中科院分区：
文献类型：
--
作者：
Hammond MD;Ambler WG;Ai Y;Sansing LH
脑出血(ICH)后很快就会出现炎症反应。这种反应的一个关键组成部分是白细胞在大脑中的招募，这促进了啮齿动物模型的神经损伤。然而，白细胞跨内皮细胞迁移到受损脑组织的机制尚不清楚。本研究检测了四种白细胞亚型上的白细胞黏附分子(α-4整合素、L-选择素和αLβ-2整合素)，以确定哪些在脑出血后白细胞募集中起重要作用。采用脑出血小鼠注血模型，纹状体内注射25μL血。用流式细胞仪检测脑组织和血液中白细胞的数量和黏附分子的表达。用α-4整合素封闭抗体评价α-4在白细胞迁移和神经损伤中的作用。脑出血后各白细胞α-4整合素均升高，而L-选择素无明显变化，αLβ-2仅在T细胞上升高。拮抗α-4可减少白细胞迁移，减轻神经行为功能障碍。α-4整合素是一种重要的细胞黏附分子，参与脑出血后的神经炎症反应。
Intracerebral hemorrhage (ICH) is swiftly followed by an inflammatory response. A key component of this response is the recruitment of leukocytes into the brain, which promote neurological injury in rodent models. However, the mechanisms by which leukocytes transmigrate across the endothelium into the injured brain are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-selectin, and αLβ2 integrin) on four leukocyte subtypes to determine which are important for leukocyte recruitment after ICH. We used the blood injection mouse model of ICH, whereby 25 μl of blood were injected into the striatum. Flow cytometry was used to quantify leukocyte populations and adhesion molecule expression in brain and blood. An α4 integrin blocking antibody was administered to evaluate the contribution of α4 in leukocyte migration and neurological injury. α4 integrin was elevated on all leukocyte populations in brain after ICH, whereas L-selectin was unchanged and αLβ2 was increased only on T cells. Antagonism of α4 resulted in decreased leukocyte transmigration and lessened neurobehavioral disability. α4 integrin is an important cell adhesion molecule involved in neuroinflammation following ICH.