Diphteria toxin

Uherek, C., Fominaya, J. and Weis, W. (1998) A modular DNA carrier protein based on the structure of diphteria toxin mediates target cell-specific gene delivery. J. Biol Chem., 273, 8835-8841. 

In the mammalian cell mutation test CHL cells are exposed to the test compound for 3 h with and without the metabolic activation system. After 7 days of culture, diphtheria toxine is added and the cells are left again to culture for another 7 days until the nmnber of diphteria toxin resistent colonies are scored. 

Foley T, Moehring JM, Moehring TJ (1995) Mutations in the elongation factor 2 gene which confer resistance to diphteria toxin and Pseudomonas exotoxin A. J Biol Chem 270 23218-23225. 

An interesting attempt has been made to treat viral diseases with the liposome-encapsulated fragment A of diphteria toxin. It has been shown in cell culture experiments (cells infected with the virus of sclerosing panencephalitis), that the liposome-immobilized A fragment decreases cell infection by 99%, whereas the free fragment itself does not influence infected cells at all. 

Enhancement of immune responses to T independent antigens such as bacterial polysaccharides need the conjugation of the antigens to a carrier such as a diphteria toxin or keyhole limpet hemocyanin (KLH) in order to provide T cell help to the polysaccharide [14]. However, experiments have demonstrated that certain strains of mice had significantly enhanced serum antibody titers to an unconjugated . coli polysaccharide (60 xg/dose) when QS-21 (15 Xg/dose) was used. The titer increase was largely a result of increased levels of IgG2b subclass antibodies [24]. 

Several highly immunogenic bacterial proteins have been proposed as carriers for conjugate vaccines. The list includes bacterial pili, outer membrane proteins (OMPs), and excreted toxins of pathogenic bacteria [105], preferably in toxoid fomr Tetanus and diphteria toxoids, which are readily available and accepted for human use, are the preferred carrier despite the lot-to-lot variations during the detoxification procedure. 

The barrier effect is mainly due to the fact that the cells lining the walls of the capillaries present in the brain tissue are tightly joined, contrary to what prevails with capillaries in other tissues this leaves very little space between the cells for filtration of small-size, water-soluble molecules. Moreover, the cells of brain capillaries possess very few endocytotic vesicles, which in capillaries of other tissues engulf large molecules and serve as a transfer mechanism as a result, many neurotoxins, such as diphteria and tetanus toxins, are excluded. Furthermore, the capillaries of the brain are surrounded by prolongations of certain brain cells, thus forcing lipid-soluble chemicals to cross an additional lipid membrane. Finally, the intercellular fluid bathing the brain cells contains lower concentrations of proteins this results in a reduction of the movement of certain water-insoluble chemicals that are more easily transported when bound to proteins. 

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