title: The cytotoxic effect of anthrax lethal toxin on human lung cells in vitro and the protective action of bovine antibodies to PA and LF.
abstract: The excretion of protein toxins by vegetative cells of Bacillus anthracis is critical to the development of the lethal consequences of anthrax, particularly inhalational anthrax. Whilst the lung macrophages and other phagocytic cells transfer the spores from the lung cavities into the lymphatic system, and provide an initial germination site for the proliferation of the vegetative cells, it appears that much of the tissue pathology at the time of the host's death could be due to the action of the toxins, especially lethal toxin-protective antigen (PA) plus lethal factor (LF). The widespread tissue oedema and hypoxia may in part reflect a direct attack by lethal toxin on vascular endothelial cells. Also the distribution of the receptor for PA on a variety of cell types including epithelial cells as well as endothelial cells, and the involvement of the lungs in the pathology raises the question of whether lung epithelial cells are also susceptible to lethal toxin. To investigate this possibility a series of in vitro cytotoxicity experiments were carried out with human lung epithelial cells and microvascular endothelial cells. In these experiments lethal toxin (PA 500 ng ml(-1) plus 10-100 ng ml(-1) LF) was shown to cause a progressive loss of cell viability that developed slowly over at least 3 days. Affinity purified bovine colostrum antibodies for both PA and LF were equally effective in providing a 100% protection for epithelial cells from this cytotoxic action of lethal toxin. This was achieved at a 10:1 molar ratio of the particular antibody to its respective target.
authors.affiliation: Defence Science and Technology Organisation, 506 Lorimer Street, Fishermans Bend, Victoria 3207, Australia. Brian.Paddle@dsto.defence.gov.au
authors.forename: Brian M
authors.initials: BM
authors.lastname: Paddle
authors.forename: Victor K
authors.initials: VK
authors.lastname: Wong
authors.forename: Brian D
authors.initials: BD
authors.lastname: Muller
mesh_terms: D000818:Animals; D000906:Antibodies / Q000302:isolation & purification / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity*; D001427:Bacterial Toxins / Q000276:immunology* / Q000633:toxicity*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003126:Colostrum / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009500:Neutralization Tests
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin