Title: Human aortic endothelial cells compare favourably with macrophages for the study of anthrax toxins

Authors: Hun Seok Lee; Su Yeun Lee; Nirmal Rajasekaran; Hae Eun Joe; Young Kee Shin; Sung Min Kim; Sang Gyu Park; Tae Jin Kang; Jee Cheon Kim

Addresses: Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Sensory Research Center, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea ' Department of Biomedical Science, CHA Stem Cell Institute, CHA University, Gyunggido 463-840, Korea ' College of Pharmacy, Sahmyook University, Seoul 139-742, Korea ' Agency for Defense Development, Daejeon 305-152, Korea

Abstract: Anthrax is an infectious disease caused by Bacillus anthracis. Although B. anthracis is rare in the natural environment, anthrax spores can be produced in vitro and potentially used as a biological weapon. Thus, understanding the molecular pathogenesis of anthrax is a critical concern for national security. The aim of this study was to compare the effects of anthrax toxins, lethal toxin (LeTx), and edema toxin (EdTx) on human aortic endothelial cells (HAECs) and the J774A.1 murine macrophage cell line. We analysed cell viability, adhesion, morphology, and lipopolysaccharide (LPS)-stimulated cytokine production after incubation of cells with varying concentrations of the toxins. Both LeTx and EdTx markedly inhibited LPS-induced transcription of tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 in J774A.1 cells. In contrast, EdTx synergised with LPS to increase the transcription of IL-6 and IL-8 in HAECs. We showed that HAECs are suitable for anthrax toxin research and express higher levels of the two anthrax toxin receptors - tumour endothelial marker 8 (TEM8/ANTXR1) and capillary morphogenesis protein 2 (CMG2/ANTXR2) - than do J774A.1 cells. Collectively, our results suggest that HAECs may be superior to macrophages for the study of anthrax pathogenesis.

Keywords: anthrax toxins; protective antigens; lethal toxin; edema toxin; macrophages; human aortic endothelial cells; biological weapons; cell viability; adhesion; morphology; lipopolysaccharide stimulated cytokine production; anthrax pathogenesis.

DOI: 10.1504/IJNT.2013.054216

International Journal of Nanotechnology, 2013 Vol.10 No.8/9, pp.756 - 770

Published online: 01 Aug 2013 *

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