Marques Natália Cassaro, Mo Reira Pamela Rodrigues Reina, Bertolo Paulo Henrique Leal, Gava Fábio Nelson, Vasconcelos Rosemeri de Oliveira
Departamento de Patologia Veterinária, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista (UNESP) , Via de Acesso Prof. Paulo Donato Castellane, s / n , Jaboticabal , SP , 14884-900 , Brasil.
Universidade do Mississipi Medical Center , Jackson , MS, USA.
Parasitol Res. 2018 Jun;117(6):1829-1837. doi: 10.1007/s00436-018-5870-2. Epub 2018 Apr 27.
Hepatic stellate cells (HSC), or Ito cells, store vitamin A when at rest but undergo phenotypic changes in situations of liver injury, which may induce fibrosis, and they may participate in the immune response in the liver. The objective of the present study was to investigate the role of HSC in the livers of dogs with visceral leishmaniasis (VL). Twenty-eight livers from dogs infected with VL that were living in an area endemic for the disease were evaluated, among which 13 were asymptomatic (A) and 15 were symptomatic (S). A control group (C) was formed by five dogs from an area that was not endemic for VL. These organs were subjected to histopathological analysis (Masson's trichrome for fibrosis) and immunohistochemical analysis (Leishmania, smooth-muscle α-actin and TGF-β). In the livers from the symptomatic dogs, a moderate to severe granulomatous inflammatory reaction was observed in the capsule and in the portal, centrilobular and intralobular regions. In the asymptomatic dogs, there was slight to moderate presence of granulomas, and these were even absent in some dogs. The intensity of hepatic fibrosis was predominantly low in the infected dogs (A and S), and fibrosis was absent in the control group. The immunomarking of HSC in the infected groups (A and S) differed significantly (P = 0.0153) from that of the control group. The symptomatic dogs presented the largest number of positive cells. This group also presented a larger number of parasitized macrophages, but did not differ statistically from the asymptomatic group (P > 0.05). The cytokine TGF-β was only detected at low levels, and only in the infected animals, but this did not differ from the control group. Immunomarking for HSC was observed mainly in the nuclei of cells present in the hepatic granulomas of symptomatic dogs and in the sinusoids of the asymptomatic dogs. It was concluded that in the livers of dogs with VL, the HSC are activated and participate in the hepatic response to the parasite. The cytokine TGF-β may be involved in this activation, but in the chronic phase of the infection, this cytokine was detected at lower proportions. It is possible that HSC may also contribute towards chemotaxis of leukocytes for the hepatic compartment, along with other cell types such as Kupffer cells.
肝星状细胞（HSC），即伊托细胞，在静止时储存维生素A，但在肝损伤情况下会发生表型变化，这可能会诱发肝纤维化，并且它们可能参与肝脏的免疫反应。本研究的目的是调查HSC在患内脏利什曼病（VL）犬肝脏中的作用。对生活在该病流行地区的28只感染VL的犬的肝脏进行了评估，其中13只为无症状（A）犬，15只为有症状（S）犬。一个对照组（C）由来自非VL流行地区的5只犬组成。对这些器官进行了组织病理学分析（用Masson三色染色法检测纤维化）和免疫组织化学分析（检测利什曼原虫、平滑肌α肌动蛋白和转化生长因子-β）。在有症状犬的肝脏中，在包膜以及门静脉、小叶中心和小叶内区域观察到中度至重度的肉芽肿性炎症反应。在无症状犬中，肉芽肿的存在程度为轻度至中度，有些犬甚至没有肉芽肿。感染犬（A组和S组）的肝纤维化程度主要较低，对照组则无纤维化。感染组（A组和S组）HSC的免疫标记与对照组有显著差异（P = 0.0153）。有症状犬的阳性细胞数量最多。该组还存在较多被寄生的巨噬细胞，但与无症状组相比无统计学差异（P > 0.05）。细胞因子转化生长因子-β仅在感染动物中低水平检测到，但与对照组无差异。HSC的免疫标记主要在有症状犬肝脏肉芽肿中的细胞核以及无症状犬的肝血窦中观察到。得出的结论是，在患VL犬的肝脏中，HSC被激活并参与肝脏对寄生虫的反应。细胞因子转化生长因子-β可能参与了这种激活，但在感染的慢性期，该细胞因子的检测比例较低。HSC可能还与库普弗细胞等其他细胞类型一起，促进白细胞向肝区的趋化作用。
