Yoshimoto T
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1997 Jan;72(1):97-112.
With a hypothesis that an inflammatory cascade composed of cell-to-cell interactions causes cellular damage secondary to reperfusion, I studied the temporary profiles of expression of intracellular adhesion molecule (ICAM)-1 and associating induction of proinflammatory cytokines in an acute phase following reperfusion of rat forebrain. Immunohistologically, ICAM-1 expression began to increase 1 hr after reperfusion in the microvessels of the subcortical region and the basal ganglia. Also, leukocyte positive of lymphocyte function associated antigen (LFA)-1 appeared attached to the capillary vessel walls 6 hrs after reperfusion. Semiquantitatively calibrated RT-PCR analysis was employed to assess the relative expression of mRNA. Increase of the mRNAs from the basal levels after reperfusion followed two different patterns; one, seen for ICAM-1, interleukin (IL)-1 alpha, beta, tumor necrosis factor (TNF)-alpha, and monocyte-chemoattractant protein (MCP)-1, exhibited an increase as early as 1 hr, and another, for IL-6 and macrophage migration inhibitory factor (MIF), showed a gradual increase up to 24 hr after reperfusion. The results were consistent with the proinflammatory properties of those immediately-induced cytokines, which may be involved in the initiation step of the inflammatory cascade, causing the secondary cellular responses. Furthermore, I found that MIF protein was expressed in neuropils in the cortex and basal ganglia by immunohistochemistry. Although precise pathophysiological role of MIF is still unclear, this protein may modulate immune reaction by leukocytes in secondary tissue damage following reperfusion stress. Clinically, I investigated soluble ICAM-1 in sera of patients with various cerebral ischemic diseases of acute stage (n = 28) and healthy adults (n = 23). The serum levels of sICAM-1 in patients with ischemic diseases, particularly with transient ischemic attack (TIA), were significantly higher (p < 0.01) than those of healthy individuals. These results together indicate that cell-cell interaction by adhesion molecules and cytokines is an important component in the pathogenesis of ischemic cerebral diseases, especially at the acute phase.
基于一种假设，即由细胞间相互作用组成的炎症级联反应会导致再灌注继发的细胞损伤，我研究了大鼠前脑再灌注急性期细胞间黏附分子（ICAM）-1的表达临时图谱以及促炎细胞因子的相关诱导情况。免疫组织化学结果显示，再灌注1小时后，皮质下区域和基底神经节微血管中的ICAM-1表达开始增加。此外，再灌注6小时后，淋巴细胞功能相关抗原（LFA）-1阳性的白细胞似乎附着在毛细血管壁上。采用半定量校准的逆转录聚合酶链反应（RT-PCR）分析来评估mRNA的相对表达。再灌注后mRNA从基础水平的增加呈现出两种不同模式；一种模式见于ICAM-1、白细胞介素（IL）-1α、β、肿瘤坏死因子（TNF）-α和单核细胞趋化蛋白（MCP）-1，早在1小时就出现增加，另一种模式见于IL-6和巨噬细胞迁移抑制因子（MIF），在再灌注后24小时逐渐增加。这些结果与那些立即诱导的细胞因子的促炎特性一致，这些细胞因子可能参与炎症级联反应的起始步骤，导致继发性细胞反应。此外，我通过免疫组织化学发现MIF蛋白在皮质和基底神经节的神经毡中表达。尽管MIF的确切病理生理作用仍不清楚，但这种蛋白可能在再灌注应激后的继发性组织损伤中调节白细胞的免疫反应。临床上，我研究了急性期各种脑缺血疾病患者（n = 28）和健康成年人（n = 23）血清中的可溶性ICAM-1。缺血性疾病患者，尤其是短暂性脑缺血发作（TIA）患者的血清sICAM-1水平显著高于健康个体（p < 0.01）。这些结果共同表明，黏附分子和细胞因子介导的细胞间相互作用是缺血性脑疾病发病机制中的一个重要组成部分，尤其是在急性期。
