Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis
Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis
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DOI：
10.4049/jimmunol.172.1.45
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发表时间：
2004-01-01
影响因子：
4.4
通讯作者：
Swain, MG
中科院分区：
文献类型：
--
作者：
Bonder, CS;Ajuebor, MN;Swain, MG
白细胞浸润肝脏对于肝炎肝损伤的发展至关重要。小鼠服用Con A后发生的肝炎被认为是一种T淋巴细胞介导的疾病。在本研究中，我们报告中性粒细胞是Con A引起的淋巴细胞募集和肝损伤的关键启动子。本研究的目的是通过活体显微镜研究中性粒细胞在体内Con A诱导的肝炎中的参与情况。给予Con A后，我们观察到白细胞滚动通量显着增加，滚动速度降低，白细胞对肝微血管的粘附增加。荧光显微镜发现，在 Con A 给药 4 小时内，只有少数招募的白细胞是 T 淋巴细胞。此外，免疫组织化学显示，Con A 治疗后，招募到肝脏的中性粒细胞显着增加，这与肝细胞损伤有关，血清丙氨酸转氨酶水平升高就反映了这一点。使用流式细胞术，我们观察到 Con A 可以直接与中性粒细胞结合，从而导致 L-选择素脱落、β(2)-整合素表达增加以及活性氧化剂的产生。中性粒细胞耗竭后，Con A 诱导的 CD4+ T 淋巴细胞募集至肝脏的显着抑制导致肝损伤完全减轻（通过血清丙氨酸转氨酶水平进行评估）。总之，目前的数据支持这样的概念，即中性粒细胞在控制 Con A 诱导的 CD4(+) T 细胞募集到肝脏以及随后的肝炎发展中发挥着重要的、以前未被认识到的作用。
Leukocyte infiltration into the liver is paramount to the development of liver injury in hepatitis. Hepatitis occurring after the administration of Con A in mice is felt to be a T lymphocyte-mediated disease. In this study, we report that neutrophils are the key initiators of lymphocyte recruitment and liver injury caused by Con A. The objectives of this study were to investigate the involvement of neutrophils in Con A-induced hepatitis in vivo via intravital microscopy. After Con A administration, we observed a significant increase in leukocyte rolling flux, a decrease in rolling velocity, and an increase in leukocyte adhesion to the hepatic microvasculature. Fluorescence microscopy identified that within 4 h of Con A administration only a minority of the recruited leukocytes were T lymphocytes. Furthermore, immunohistochemistry showed a significant increase in neutrophils recruited to the liver post-Con A treatment in association with liver cell damage, as reflected by elevated serum alanine aminotransferase levels. Using flow cytometry, we observed that Con A could bind directly to neutrophils, which resulted in a shedding of L-selectin, an increase in beta(2)-integrin expression, and the production of reactive oxidants. Following neutrophil depletion, a significant inhibition of Con A-induced CD4(+) T lymphocyte recruitment to the liver resulted and complete reduction in, hepatic injury, as assessed by serum alanine aminotransferase levels. In summary, the present data support the concept that neutrophils play an important and previously unrecognized role in governing Con A-induced CD4(+) T cell recruitment to the liver and the subsequent development of hepatitis.