Palacios-Macapagal Daphne, Connor Jane, Mustelin Tomas, Ramalingam Thirumalai R, Wynn Thomas A, Davidson Todd S
MedImmune, Gaithersburg, MD 20878; and.
National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 2017 Aug 1;199(3):847-853. doi: 10.4049/jimmunol.1601162. Epub 2017 Jun 26.
Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of -infected mice. eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death.
许多慢性肝脏疾病的特征是免疫反应失调和肝细胞死亡。我们使用体内模型研究对坏死性肝损伤的免疫反应，发现坏死的肝细胞会诱导嗜酸性粒细胞募集。坏死肝脏诱导嗜酸性粒细胞分泌白细胞介素-1β和白细胞介素-18、脱颗粒以及细胞死亡。半胱天冬酶-1抑制剂可阻断所有这些反应。半胱天冬酶-1介导的细胞死亡以及伴随的细胞因子释放是一种称为细胞焦亡的新型细胞死亡形式的标志。为了在疾病模型中证实这种反应，我们从小鼠肝脏中分离出嗜酸性粒细胞。虫卵寄生于感染小鼠的肝血窦中，导致肝细胞死亡、炎症和进行性肝纤维化。这种反应的典型特征是大量嗜酸性粒细胞增多，并且我们能够在浸润的嗜酸性粒细胞中证实细胞焦亡。这表明细胞焦亡是嗜酸性粒细胞响应大规模肝细胞死亡而使用的一种细胞途径。
