Ohmi K, Kiyokawa N, Takeda T, Fujimoto J
Department of Pathology, Department of Infectious Diseases Research, National Children's Medical Reseach Center, 3-35-31, Taishido, Setagaya-ku, Tokyo, 154-8509, Japan.
Biochem Biophys Res Commun. 1998 Oct 9;251(1):137-41. doi: 10.1006/bbrc.1998.9417.
We show here that the susceptibility of endothelial cells to Shiga toxin (Stx)s differs remarkably depending on their cellular origins. The concentration of Stx-1 required to reduce cell viability by 50% as measured by MTT assay was 30 and 300 fM for neonatal and adult human microvascular endothelial cells (HMVEC), respectively, and 30 pM for human coronary artery endothelial cells (HCAEC). Human umbilical venous endothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC) showed no sensitivities to Stx-1. Surprisingly, Stx-2 was approximately 10-100 times more toxic to HMVEC than Stx-1. Moreover sodium butyrate sensitized HMVEC by 100-fold to the cytotoxic activity of Stxs. These results were found to reflect the amount of Gb3/CD77 on the cell surface on a per cell basis using flow cytometrical analysis. The high sensitivity of HMVEC to Stxs suggests their involvement in the pathogenesis of organ failure induced by Stx-producing Escherichia coli.
我们在此表明，内皮细胞对志贺毒素（Stx）的敏感性因其细胞来源不同而有显著差异。通过MTT法测定，使新生和成人人类微血管内皮细胞（HMVEC）的细胞活力降低50%所需的Stx-1浓度分别为30和300 fM，而人类冠状动脉内皮细胞（HCAEC）则为30 pM。人脐静脉内皮细胞（HUVEC）和牛主动脉内皮细胞（BAEC）对Stx-1不敏感。令人惊讶的是，Stx-2对HMVEC的毒性比对Stx-1高约10 - 100倍。此外，丁酸钠使HMVEC对Stxs的细胞毒性活性敏感100倍。使用流式细胞术分析发现，这些结果反映了每个细胞表面Gb3/CD77的量。HMVEC对Stxs的高敏感性表明它们参与了由产志贺毒素大肠杆菌引起的器官衰竭的发病机制。
