LEUKOCYTE ADHESION MOLECULES IN THE LIVER AND PLASMA CYTOKINE LEVELS IN ENDOTOXIN-INDUCED RAT-LIVER INJURY
LEUKOCYTE ADHESION MOLECULES IN THE LIVER AND PLASMA CYTOKINE LEVELS IN ENDOTOXIN-INDUCED RAT-LIVER INJURY
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DOI：
10.3109/00365529509096349
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发表时间：
1995-10-01
影响因子：
1.9
通讯作者：
KASUKAWA, R
中科院分区：
文献类型：
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作者：
OHIRA, H;UENO, T;KASUKAWA, R
背景：已知多形核中性粒细胞（PMNs）和窦状内皮细胞（SECs）之间的相互作用参与了急性肝损伤的发病机制。也有报道称，肿瘤坏死因子- α (tnf - α)上调SECs上ICAM-1的表达，白细胞介素-8 （IL-8）可促进PMNs上CD11/CD18的快速激活。这些发现扩展到脂多糖（LPS）诱导大鼠肝损伤后肝组织中白细胞粘附分子（ICAM-1、CD11a/CD18和CD11b/CD18）表达与血浆TNF和IL-8水平的关系。方法：雄性Wistar大鼠体重200 ~ 250 g，静脉注射LPS 2 mg /kg， 0.2 ~ 0.25 ml。在LPS暴露后1、3、8和12小时采集肝脏和血液样本。分别采用生物测定法和特异性酶联免疫吸附法测定血浆TNF和IL-8水平。肝脏标本固定，免疫组化使用特异性单克隆抗体ICAM-1、CD11a和CD11b进行研究。结果：LPS暴露后1 h TNF水平达到峰值（23.3 +/- 11.4 IU/ml）， 3 h IL-8水平达到峰值（343.1 +/- 110.5 ng/ml）。早在Ih就观察到肝脏中pmn数量的增加，并持续到LPS暴露后12小时。pmn粘附于退行性SECs和肝细胞。8 h时，SECs上的ICAM-1呈弥散性强表达，附着于SECs的PMNs同时表达CD11a和CD11b。肝细胞上也可见到ICAM-1。结论：PMN-SEC与pmn -肝细胞通过白细胞粘附分子相互作用，与TNF、IL-8等炎性细胞因子相关，在急性肝损伤的发病机制中存在并发挥重要作用。
Background: The interactions between polymorphonuclear neutrophils (PMNs) and sinusoidal endothelial cells (SECs) have been known to be involved in the pathogenesis of acute liver injury. It has been also reported that tumor necrosis factor-alpha (TNF-alpha) up-regulates ICAM-1 expression on SECs and that interleukin-8 (IL-8) provokes rapid activation of CD11/CD18 on PMNs. These findings expand into the relationship between the expression of leukocyte adhesion molecules (ICAM-1, CD11a/CD18 and CD11b/CD18) in liver tissues and plasma TNF and IL-8 levels after lipopolysaccharide (LPS)-induced liver injury in rats. Methods: Male Wistar rats weighing 200-250 g were treated with 2 mg LPS/kg intravenously in a 0.2- to 0.25-ml volume. Liver and blood samples were obtained at 1, 3, 8, and 12 h after LPS exposure. Plasma TNF and IL-8 levels were measured using bioassay and specific enzyme-linked immunosorbent assay, respectively. Liver samples were fixed and studied by immunohistochemistry using specific monoclonal antibodies against ICAM-1, CD11a, and CD11b. Results: The TNF level showed a peak at 1 h (23.3 +/- 11.4 IU/ml), and the IL-8 level showed a peak at 3 h (343.1 +/- 110.5 ng/ml) after LPS exposure. An increase in the number of PMNs in the liver was observed as early as Ih and continued until 12 h after LPS exposure. PMNs adhered to degenerated SECs and hepatocytes. ICAM-1 on SECs was diffusely and strongly expressed at 8 h, and PMNs adhered to SECs expressed both CD11a and CD11b. ICAM-1 was also observed on hepatocytes. Conclusion: These data suggest that PMN-SEC and PMN-hepatocyte interactions via leukocyte adhesion molecules, related to inflammatory cytokines such as TNF and IL-8, exist and play an important role in the pathogenesis of acute liver injury.