Yao C, Bohnet S, Jasmer D P
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman 99164-7040, USA.
Mol Biochem Parasitol. 1998 Oct 30;96(1-2):1-13. doi: 10.1016/s0166-6851(98)00082-6.
Infection by the parasitic nematode Trichinella spiralis induces cell cycle repositioning (chronic suspension in apparent G2/M) and genetic reprogramming in differentiated mammalian skeletal muscle cells. These changes occur in association with dramatic enlargement of infected host cell nuclei (as large as 17 microm in diameter) and nucleoli. Nuclear antigens (NA) that colocalize with host chromatin have been detected by antibodies to T. spiralis antigens, but the functions of these NA are unresolved. Mebendazole (MBZ) preferentially binds parasite versus host beta-tubulins, is implicated in inhibiting secretion in nematodes and induces cytoplasmic changes in muscle cells infected with T. spiralis. These infected cell changes might be indirect via MBZ inhibition of parasite secretions. This effect would have implications for host/parasite interactions and was evaluated here. MBZ treatment of chronically infected mice caused: (1) a significant deformation of host nuclei and diminution of nucleoli by 4 and 6 days of treatment (dot), respectively; (2) a reduction of nuclear lamins A/C in infected cell nuclei that was concomitant with nuclear deformation; and (3) significant reductions in total RNA, general protein and acid phosphatase activity levels. These changes were associated with the depletion of NA from host nuclei detected by 4 dot. However, DNA content of infected cell nuclei was not detectably reduced and muscle gene expression was not reactivated. The cellular changes documented are likely to account for previously described cytoplasmic alterations induced by MBZ. Concomitant depletion of NA from infected cell nuclei suggests a role of these products in regulating nuclear functions of host cells.
寄生线虫旋毛虫感染可诱导分化的哺乳动物骨骼肌细胞发生细胞周期重新定位（明显停滞于G2/M期）和基因重编程。这些变化伴随着被感染宿主细胞核（直径可达17微米）和核仁的显著增大。通过针对旋毛虫抗原的抗体已检测到与宿主染色质共定位的核抗原（NA），但这些NA的功能尚未明确。甲苯咪唑（MBZ）优先结合寄生虫而非宿主的β-微管蛋白，与抑制线虫分泌有关，并可诱导感染旋毛虫的肌肉细胞发生细胞质变化。这些受感染细胞的变化可能是MBZ抑制寄生虫分泌的间接结果。这种效应可能对宿主/寄生虫相互作用有影响，本文对此进行了评估。用MBZ处理慢性感染的小鼠导致：（1）分别在处理4天和6天时，宿主细胞核明显变形，核仁缩小；（2）感染细胞核中核纤层蛋白A/C减少，同时伴有核变形；（3）总RNA、总蛋白和酸性磷酸酶活性水平显著降低。这些变化与处理4天时检测到的宿主细胞核中NA的减少有关。然而，感染细胞核的DNA含量未检测到明显减少，肌肉基因表达也未重新激活。记录的细胞变化可能解释了先前描述的由MBZ诱导的细胞质改变。感染细胞核中NA的同时减少表明这些产物在调节宿主细胞的核功能中起作用。
