Liver Kupffer cells control the magnitude of the inflammatory response in the injured brain and spinal cord
Liver Kupffer cells control the magnitude of the inflammatory response in the injured brain and spinal cord
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DOI：
10.1016/j.neuropharm.2008.06.074
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发表时间：
2008-10-01
影响因子：
4.7
通讯作者：
Anthony, Daniel C.
中科院分区：
文献类型：
--
作者：
Campbell, Sandra J.;Zahid, Imran;Anthony, Daniel C.
中枢神经系统的炎症反应是由肝趋化因子的合成，促进白细胞增多，促进白细胞募集到损伤部位。为了了解肝脏对急性脑损伤的反应过程中肝脏中单个细胞群的作用，我们使用氯膦酸盐填充的脂质体选择性地耗尽枯否细胞（KC），并在向大鼠脑中微量注射IL-1 β或脊髓压迫损伤后评估炎症反应。我们通过免疫组织化学显示，KC耗竭使中性粒细胞浸润到IL-1 β注射的脑中减少70%，并且使中性粒细胞浸润到挫伤的脊髓中减少50%。肝脏趋化因子mRNA表达的qRT-PCR分析显示，脑损伤后肝脏中的趋化因子表达不限于单个细胞群。在非消耗大鼠中，CXCL-10、IL-1 β、CCL-2和MIP-1 α mRNA比KC消耗大鼠增加高达6倍。然而，CXCL-1和MIP-1 β并没有受到KC耗竭的显著影响。肝脏趋化因子mRNA表达的减少与中性粒细胞动员减少无关，这可能与预期无关。这些结果表明，在对CNS损伤的反应中，KC介导的机制负责增加中性粒细胞进入CNS损伤部位，但中性粒细胞动员依赖于其他非KC介导的事件。然而，KC活性的抑制可以防止急性脑损伤后的继发性损害。(c)2008爱思唯尔有限公司保留所有权利。
The CNS inflammatory response is regulated by hepatic chemokine synthesis, which promotes leukocytosis and facilitates leukocyte recruitment to the site of injury. To understand the role of the individual cell populations in the liver during the hepatic response to acute brain injury, we selectively depleted Kupffer cells (KC), using clodronate-filled liposomes, and assessed the inflammatory response following a microinjection of IL-1 beta into the rat brain or after a compression injury in the spinal cord. We show by immunohistochemistry that KC depletion reduces neutrophil infiltration into the IL-1 beta-injected brain by 70% and by 50% into the contusion-injured spinal cord. qRT-PCR analysis of hepatic chemokine mRNA expression showed that chemokine expression in the liver after brain injury is not restricted to a single cell population. In non-depleted rats, CXCL-10, IL-1 beta, CCL-2, and MIP-1 alpha mRNAs were increased up to sixfold more than in KC depleted rats. However, CXCL-1 and MIP-I beta were not significantly affected by KC depletion. The reduction in chemokine mRNA expression by the liver was not associated with decreased neutrophil mobilisation as might have been expected. These findings suggest that in response to CNS injury, KC mediated mechanisms are responsible for increasing neutrophil entry to the site of CNS injury, but that neutrophil mobilisation is dependent on other non-KC mediated events. However, the suppression of KC activity may prevent secondary damage after acute brain injury. (c) 2008 Elsevier Ltd. All rights reserved.