HUMAN MICROVASCULAR ENDOTHELIAL-CELLS ARE STRONGLY SENSITIVE TO SHIGATOXINS

We show here that the susceptibility of endothelial cells to Shiga tox in (Stx)s differs remarkably depending on their cellular origins. The concentration of Stx-1 required to reduce cell viability by 50% as mea sured by MTT assay was 30 and 300 fM for neonatal and adult human micr ovascular endothelial cells (HM-VEC), respectively, and 30 pM for huma n coronary artery endothelial. cells (HCAEC). Human umbilical venous e ndothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC) sh owed 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 surfa ce on a per cell basis using flow cytometrical analysis. The high sens itivity of HMVEC to Stxs suggests their involvement in the pathogenesi s of organ failure induced by Stx-producing Escherichia coli. (C) 1998 Academic Press.