The toxic effects of the haemorrhagic toxin of were studied in mice, rats, guinea-pigs and rabbits, and in various cultured cells. In rabbits, but not in the other animals, intradermal injection with crude toxin and its injection into a ligated intestinal loop caused haemorrhage in both the skin and intestinal wall. Intraperitoneal (i.p.) injection of crude toxin similarly caused death only of rabbits, with marked haemorrhage in the serous surface of kidney, intestines, liver, spleen, mesentery and diaphragm. Histological examination of the rabbits killed after i.p. inoculation revealed leakage of blood into a space beneath the serous membranes of parenchymatous organs in the peritoneal cavity and within the loose connective tissues in the mesentery and diaphragm. Cytotoxicity of partially purified haemorrhagic toxin was noted with rabbit aorta endothelial cells, human skin capillary vein endothelial cells and bovine pulmonary artery endothelial cells, but not with Chinese hamster ovary cells, Vero cells, human epitheloid carcinoma cells, human colon carcinoma cells (T84) and human colon adenoearcinoma cells (Caco 2). The results suggest that the haemorrhagic toxin of exerts its effects in rabbits but not in mice, rats or guinea-pigs, through direct action on endothelial cells.


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