PMID: 9172011Dec 1, 1996Paper

Ricin toxin contains three lectin sites which contribute to its in vivo toxicity

International Journal of Immunopharmacology
T FuA E Frankel

Abstract

Ricin intoxication of mammalian cells is initiated by B chain (RTB) binding to cell surface galactosides. Recombinant insect-derived RTB mutants with modifications in lectin-site subdomains 2 gamma, 1 alpha/2 gamma, and 1 alpha/1 beta/2 gamma were reassociated with plant RTA and tested for lethality in C57B1/6 6-8 weeks old mice. The LD50 of intraperitoneally injected castor bean ricin was 75 ng per 18 g mouse. The LD50 of single-site 2 gamma mutant heterodimer was 100 ng: the LD50 of the double-site 1 alpha/2 gamma mutant heterodimer was 500 ng, and the LD50 of the triple-site 1 alpha/1 beta,2 gamma mutant heterodimer was > 10 micrograms. Plant RTA alone had an LD50 of 300 micrograms. Animals died between 1 and 10 days post-injection. Histopathological examination of morbid animals receiving an LD50 dose of each toxin revealed only apoptosis in the thymus and spleen. The present data provide clear evidence for participation of three lectin sites in ricin in vivo toxicity. These results suggest an origin for some of the normal tissue toxicities observed with clinical trials of doubly blocked ricin conjugates and suggest modification of at least three RTB subdomains will be necessary in genetically engineered ricin fusion proteins.

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Citations

Mar 27, 2004·European Biophysics Journal : EBJ·Jan SunPeter Pohl
Jun 27, 2009·International Journal of Pharmaceutics·Alpesh MistryLisbeth Illum
Dec 20, 2014·PloS One·Daniel H J NgMartin J Humphries
Feb 26, 2000·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·A E FrankelE A Sausville
Oct 11, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ulisses Moreno-CelisTeresa García-Gasca
May 18, 1999·Biochemical and Biophysical Research Communications·M HelmyG Piéroni
Jun 10, 2006·Archives of Biochemistry and Biophysics·Bao-Zhong WangXin-yuan Liu
Sep 8, 2021·Cancer Cell International·Reza MahmoudiMohammad Rahmati

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