Huston C D, Houpt E R, Mann B J, Hahn C S, Petri W A
Department of Medicine, University of Virginia Health, Sciences Center, Charlottesville 22908-1340, USA.
Cell Microbiol. 2000 Dec;2(6):617-25. doi: 10.1046/j.1462-5822.2000.00085.x.
The parasite Entamoeba histolytica is named for its ability to lyse host tissues. To determine the factors responsible, we have initiated an examination of the contribution of parasite virulence factors and host caspases to cellular destruction by the parasite. Amoebic colitis in C3H/HeJ mice was associated with extensive host apoptosis at sites of E. histolytica invasion. In vitro studies of E. histolytica-Jurkat T-cell interactions demonstrated that apoptosis required contact via the amoebic Gal/GalNAc lectin, but was unaffected by 75% inhibition of the amoebic cysteine proteinases. Parasite-induced DNA fragmentation was unaffected in caspase 8-deficient Jurkat cells treated with the caspase 9 inhibitor Ac-LEHD-fmk. In contrast, caspase 3-like activity was observed within minutes of E. histolytica contact and the caspase 3 inhibitor Ac-DEVD-CHO blocked Jurkat T cell death, as measured by both DNA fragmentation and 51Cr release. These data demonstrate rapid parasite-induced activation of caspase 3-like caspases, independent of the upstream caspases 8 and 9, which is required for host cell death.
溶组织内阿米巴寄生虫因其能够裂解宿主组织而得名。为了确定其相关因素，我们已开始研究寄生虫毒力因子和宿主半胱天冬酶对寄生虫引起的细胞破坏的作用。C3H/HeJ小鼠的阿米巴结肠炎与溶组织内阿米巴侵袭部位广泛的宿主细胞凋亡有关。对溶组织内阿米巴与Jurkat T细胞相互作用的体外研究表明，细胞凋亡需要通过阿米巴的半乳糖/ N - 乙酰半乳糖胺凝集素接触，但阿米巴半胱氨酸蛋白酶75%的抑制对其没有影响。用半胱天冬酶9抑制剂Ac-LEHD-fmk处理的半胱天冬酶8缺陷型Jurkat细胞中，寄生虫诱导的DNA片段化未受影响。相反，在溶组织内阿米巴接触数分钟内观察到了半胱天冬酶3样活性，并且半胱天冬酶3抑制剂Ac-DEVD-CHO阻断了Jurkat T细胞死亡，这通过DNA片段化和51Cr释放来衡量。这些数据表明，寄生虫快速诱导了不依赖上游半胱天冬酶8和9的半胱天冬酶3样半胱天冬酶的激活，而这是宿主细胞死亡所必需的。
