Olschowka J A, Kyrkanides S, Harvey B K, O'Banion M K, Williams J P, Rubin P, Hansen J T
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, USA.
Brain Behav Immun. 1997 Dec;11(4):273-85. doi: 10.1006/brbi.1997.0506.
Injury to the central nervous system (CNS) results in inflammation, increased trafficking of leukocytes into the CNS, induction of cytokines, and exacerbation of the primary injury. The increased trafficking of neutrophils into the CNS has been described following a number of injury models including stab, stroke, and excitotoxin-induced injury. This enhanced trafficking has largely been ascribed to the adhesion molecule intercellular adhesion molecule-1 (ICAM-1, CD54). In the current study, we wished to determine if the inflammation caused by irradiation of the CNS resulted in a similar induction of ICAM-1. C3H/HeJ mice were irradiated using gamma irradiation aimed over the right cerebral hemisphere. The relative induction of ICAM-1 mRNA levels was determined using quantitative RT-PCR 6 hours following irradiation with either 0, 5, 15, 25 or 35 Gy. ICAM-1 message was seen to exhibit a normal dose response curve with increasing mRNA levels seen at 15 Gy and higher. To determine the cellular distribution of the ICAM-1 protein following irradiation, mice were sacrificed at 4 hrs, 24 hrs, 48 hrs and 7 days following 25 Gy irradiation and the tissue was processed for ICAM-1 immunocytochemistry. ICAM-1 staining was seen to increase in both endothelial cells and astrocytes beginning as early as 4 hrs. The staining intensity continued to increase throughout the 7 day period observed. Together, these results suggest that irradiation of the CNS causes a rapid induction of both ICAM-1 mRNA and protein. This suggests that increased leukocyte trafficking into the CNS may exacerbate the inflammation induced by radiation injury.
中枢神经系统（CNS）损伤会导致炎症反应、白细胞向CNS的迁移增加、细胞因子的诱导以及原发性损伤的加重。在包括刺伤、中风和兴奋性毒素诱导损伤在内的多种损伤模型后，均观察到嗜中性粒细胞向CNS的迁移增加。这种增强的迁移主要归因于黏附分子细胞间黏附分子-1（ICAM-1，CD54）。在本研究中，我们希望确定CNS照射引起的炎症是否会导致类似的ICAM-1诱导。使用γ射线照射C3H/HeJ小鼠的右大脑半球。在以0、5、15、25或35 Gy照射后6小时，使用定量RT-PCR测定ICAM-1 mRNA水平的相对诱导情况。ICAM-1信息显示出正常的剂量反应曲线，在15 Gy及更高剂量时mRNA水平升高。为了确定照射后ICAM-1蛋白的细胞分布，在25 Gy照射后的4小时、24小时、48小时和7天处死小鼠，并对组织进行ICAM-1免疫细胞化学处理。早在4小时就观察到内皮细胞和星形胶质细胞中的ICAM-1染色增加。在观察的7天期间，染色强度持续增加。总之，这些结果表明CNS照射会迅速诱导ICAM-1 mRNA和蛋白。这表明白细胞向CNS的迁移增加可能会加剧辐射损伤诱导的炎症。
