Knock-on effect of anthrax lethal toxin on macrophages potentiates cytotoxicity to endothelial cells

Microbes and Infection
Jaya Pandey, David Warburton

Abstract

Herein we report the knock-on cytotoxic effect of lethal toxin (LeTx) on human umbilical vascular endothelial cells (HUVECs). HUVECs were treated either directly with LeTx or indirectly with LeTx conditioned medium (LeTxCM) prepared from RAW264.7 macrophage cells. Cytotoxicity assays were done on HUVECs and A549 cells using LeTx. HUVECs were more susceptible to LeTx (61-74% survivals) as compared to A549 cells (83-94% survivals, P < 0.005). However, LeTxCM from RAW264.7 further potentiated killing of HUVECs (37% survival) compared to the LeTxCM from A549 cells (up to 70-100% survivals). LeTxCM challenge induced an apoptotic cell death in HUVECs, and this was confirmed by reduction of BCL-2 levels to 54%. Protective antigen (PA) binding to macrophage cell line RAW264.7 > HUVECs > A549 cells. Thus, we postulate that after the initial prodormal phase of pulmonary entry, LeTx causes not only significant direct damage to macrophages and endothelial cells, but also mediates additional indirect damage to endothelial cells mediated by a knock-on effect of LeTx on macrophages that causes apoptotic cell death in endothelial cells.

Citations

May 23, 2007·Infection and Immunity·Kaushik ChakrabartyJordan P Metcalf
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·G Jonah A RaineyJohn A T Young
Jul 30, 2009·Molecular Aspects of Medicine·Mahtab Moayeri, Stephen H Leppla
Dec 11, 2007·Cellular Microbiology·Brooke H RussellYi Xu
Oct 26, 2005·Biochemical and Biophysical Research Communications·Amber D SteeleFelice D'Agnillo
May 28, 2005·The American Journal of Pathology·Jason M WarfelFelice D'Agnillo
Jan 31, 2014·The Journal of Biological Chemistry·Johanna RiveraDavid L Goldman
Jul 12, 2007·The Journal of Biological Chemistry·Soon-Duck HaSung Ouk Kim

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