Naneh Omar, Avčin Tadej, Bedina Zavec Apolonija
Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia.
Subcell Biochem. 2014;80:221-39. doi: 10.1007/978-94-017-8881-6_11.
Natural killer (NK) cells and cytotoxic T lymphocytes (CTL) use a highly toxic pore-forming protein perforin (PFN) to destroy cells infected with intracellular pathogens and cells with pre-cancerous transformations. However, mutations of PFN and defects in its expression can cause an abnormal function of the immune system and difficulties in elimination of altered cells. As discussed in this chapter, deficiency of PFN due to the mutations of its gene, PFN1, can be associated with malignancies and severe immune disorders such as familial hemophagocytic lymphohistiocytosis (FHL) and macrophage activation syndrome. On the other hand, overactivity of PFN can turn the immune system against autologous cells resulting in other diseases such as systemic lupus erythematosus, polymyositis, rheumatoid arthritis and cutaneous inflammation. PFN also has a crucial role in the cellular rejection of solid organ allografts and destruction of pancreatic β-cells resulting in type 1 diabetes. These facts highlight the importance of understanding the biochemical characteristics of PFN.
自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）利用一种剧毒的成孔蛋白穿孔素（PFN）来破坏感染细胞内病原体的细胞以及发生癌前转化的细胞。然而，PFN的突变及其表达缺陷可导致免疫系统功能异常，并难以清除发生改变的细胞。如本章所述，由于其基因PFN1发生突变导致的PFN缺乏，可能与恶性肿瘤和严重免疫紊乱有关，如家族性噬血细胞性淋巴组织细胞增生症（FHL）和巨噬细胞活化综合征。另一方面，PFN活性过高会使免疫系统攻击自体细胞，从而导致其他疾病，如系统性红斑狼疮、多发性肌炎、类风湿性关节炎和皮肤炎症。PFN在实体器官同种异体移植的细胞排斥反应以及导致1型糖尿病的胰腺β细胞破坏中也起着关键作用。这些事实凸显了了解PFN生化特性的重要性。
