| Summary: | The pathogenesis of Clostridium welchii type D epsilon toxin intoxication has been investigated in mice and sheep with special reference to nouropathology. High concentrations of epsilon toxin in the gut of sheep cause enterotoxaemia/pulpy kidney disease and may also cause a focal symmetrical encephalomalacia (FSE). Brains from sheep dead from pulpy kidney disease were examined histologically. No brain was devoid of lesions although the severity varied considerably; one third had sufficient foci of malaoia to justify a diagnosis of FSE. Similar lesions were produced experimentally by injecting lambs with epsilon toxin and it was shown that there was initially a breakdown of the blood brain barrier. In mice it was found that this breakdown of the blood brain barrier could be prevented by the prior administration of formalinised epsilon prototoxin. It was concluded that epsilon toxin causes its effect by binding to specific receptor sites and that the prototoxin competes for these sites. With isotope-labelled prototoxin it was shown that receptor sites for the toxin existed in the brain, kidneys, heart, liver and spleen of mice. Immunoperoxidase studies showed that these were situated on the luminal surfaces of vascular endothelial cells and certain renal tubules. Similar results were obtained in lambs. The effect of epsilon toxin on the lympho-reticular system was investigated. It was found that toxin killed guinea pig liquid paraffin induced peritoneal macrophages and it was also shown that the receptor sites for epsilon toxin were probably situated on the surface of the cells. It was found that epsilon toxin increased the permeability of blood vessels in guinea pig skin as do several other bacterial toxins which are known to stimulate cyclic adenocine 30, 50- monophoaphate (CAMP) production. Also plasma cAMP concentrations in mice treated with epsilon toxin rose significantly. It was concluded that Clostridium welchii type D epsilon toxin causes widespread damage, after its absorption from the gut lumen, by binding to specific receptor sites on the surface of curtain cells where it stimulates adenyl cyclone to produce increased amounts of cAMP.
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