Mabon P J, Weaver L C, Dekaban G A
The Neurodegeneration Research Group, The John P. Robarts Research Institute, London, Ontario, N6A 5K8, Canada.
Exp Neurol. 2000 Nov;166(1):52-64. doi: 10.1006/exnr.2000.7488.
The inflammatory response that ensues during the initial 48 to 72 h after spinal cord injury causes considerable secondary damage to neurons and glia. Infiltration of proinflammatory-activated neutrophils and monocytes/macrophages into the cord contributes to spinal cord injury-associated secondary damage. beta2 integrins play an essential role in leukocyte trafficking and activation and arbitrate cell-cell interactions during inflammation. The beta2 integrin, alphaDbeta2, is expressed on monocytes/macrophages and neutrophils and binds to vascular adhesion molecule-1 (VCAM-1). The increased expression of VCAM-1 during central nervous system (CNS) inflammation likely contributes to leukocyte extravasation into the CNS. Accordingly, blocking the interaction between alphaDbeta2 and VCAM-1 may attenuate the inflammatory response at the SCI site. We investigated whether the administration of monoclonal antibodies (mAbs) specific for the rat alphaD subunit would reduce the inflammatory response after a spinal cord transection injury in rats. At a 1 mg/kg dose two of three anti-alphaD mAbs caused a significant ( approximately 65%) reduction in the number of macrophages at the injury site and one anti-alphaD mAb led to a approximately 43% reduction in the number of neutrophils at the SCI site. Thus, our results support the concept that the alphaDbeta2 integrins play an important role in the trafficking of leukocytes to a site of central nervous system inflammation. This study also offers preliminary evidence that anti-alphaD mAbs can reduce the extravasation of macrophages and, to a lesser extent, neutrophils, to the SCI site.
脊髓损伤后最初48至72小时内发生的炎症反应会对神经元和神经胶质造成相当大的继发性损伤。促炎激活的中性粒细胞和单核细胞/巨噬细胞浸润到脊髓中会导致与脊髓损伤相关的继发性损伤。β2整合素在白细胞运输和激活中起重要作用，并在炎症过程中调节细胞间相互作用。β2整合素αDβ2在单核细胞/巨噬细胞和中性粒细胞上表达，并与血管细胞黏附分子-1（VCAM-1）结合。中枢神经系统（CNS）炎症期间VCAM-1表达的增加可能有助于白细胞渗入CNS。因此，阻断αDβ2与VCAM-1之间的相互作用可能会减轻脊髓损伤部位的炎症反应。我们研究了给予大鼠αD亚基特异性单克隆抗体（mAb）是否会减少大鼠脊髓横断损伤后的炎症反应。在1mg/kg剂量下，三种抗αD mAb中的两种使损伤部位的巨噬细胞数量显著减少（约65%），一种抗αD mAb使脊髓损伤部位的中性粒细胞数量减少约43%。因此，我们的结果支持αDβ2整合素在白细胞向中枢神经系统炎症部位运输中起重要作用这一概念。本研究还提供了初步证据，表明抗αD mAb可以减少巨噬细胞向脊髓损伤部位的渗出，并在较小程度上减少中性粒细胞的渗出。
