Pinto M A, Marchevsky R S, Pelajo-Machado M, Santiago M A, Pissurno J W, França M S, Baptista M L, Gouvea A S, Santana A A, Bertho A L, Schatzmayr H G, Gaspar A M, Kubelka C F
Department of Virology, IOC/FIOCRUZ, Rio de Janeiro, Brazil.
Exp Toxicol Pathol. 2000 Mar;52(1):3-10. doi: 10.1016/S0940-2993(00)80006-8.
Callithrix jacchus is considered a reliable animal model for hepatitis A virus (HAV) infection. All three HAV orally inoculated marmosets developed hepatitis - the infection was monitored by continuous virus shedding, high levels of serum enzyme alanine aminotransferase, specific antibody and seroconversion 3-6 weeks after HAV inoculation. HAV antigen was detected in liver by immunofluorescence 4 days post inoculation (PI) and onwards. To gain insight into the biological role of inducible nitric oxide synthase (iNOS) during immune-related acute liver injury the enzyme was searched in frozen biopsies: immunofluorescent labeling was found in the cytoplasm of liver cells mainly Kupffer's cells and spleen macrophages (CD68+) starting 11 days PI with maximum intensity on the fifth to sixth week PI. Necroinflammatory liver lesions characteristic of viral hepatitis were also observed at 10 days PI with maximum severity at 4 to 6 weeks PI. Furthermore, T lymphocytes (CD2+) were raised at this time point. No difference was evident in the frequency of B lymphocytes (CD20+). Therefore, iNOS expression preceded necroinflammatory liver lesion and maximal immunofluorescence reaction was coincident with tissue injury, supporting the hypothesis that NO contributes to hepatic cytotoxic mechanism but also to virus clearance. The concomitant rise in T-lymphocyte population may suggest a role for these cells in this and/or other independent HAV-induced pathological changes.
狨猴被认为是甲型肝炎病毒（HAV）感染的可靠动物模型。所有三只经口接种HAV的狨猴均发生了肝炎——通过持续的病毒排出、高水平的血清酶丙氨酸转氨酶、特异性抗体以及接种HAV后3 - 6周的血清转化来监测感染情况。接种后4天及以后，通过免疫荧光在肝脏中检测到HAV抗原。为了深入了解诱导型一氧化氮合酶（iNOS）在免疫相关急性肝损伤中的生物学作用，在冷冻活检组织中检测该酶：从接种后11天开始，在肝细胞的细胞质中发现免疫荧光标记，主要是库普弗细胞和脾脏巨噬细胞（CD68 +），在接种后第五至六周强度最大。在接种后10天也观察到了病毒性肝炎特有的坏死性炎症性肝损伤，在接种后4至6周严重程度最高。此外，此时T淋巴细胞（CD2 +）数量增加。B淋巴细胞（CD20 +）的频率没有明显差异。因此，iNOS表达先于坏死性炎症性肝损伤，最大免疫荧光反应与组织损伤同时发生，支持了NO有助于肝脏细胞毒性机制但也有助于病毒清除的假说。T淋巴细胞群体同时增加可能表明这些细胞在这种和/或其他独立的HAV诱导的病理变化中起作用。
