Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab')2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab')2 when compared at the same molar conc...

Cells expressing ricin B chain within the secretory pathway are significantly more resistant to intoxication by ricin holotoxin but not to other cytotoxins that exploit similar endocytic routes to the cytosol. Furthermore, cells expressing the related B chain of abrin are protected against both incoming abrin and ricin. These phenotypes can be correlated with the abilities of the respective B c...

Ricin is a potent A-B toxin that is transported from the cell surface to the cytosol, where it inactivates ribosomes, leading to cell death. Ricin enters cells via endocytosis, where only a minute number of ricin molecules reach the endoplasmic reticulum (ER) lumen. Subsequently, the ricin A chain traverses the ER bilayer by a process referred to as dislocation or retrograde translocation to ga...

BACKGROUND Ricin is a lethal toxin that inhibits protein synthesis. It is easily extracted from a ubiquitously grown plant, Ricinus communis, and thus readily available for use as a bioweapon (BW). Anti-ricin antibodies provide the only known therapeutic against ricin intoxication. RESULTS In this study, after immunizing a non-human primate (Macaca fascicularis) with the ricin chain A (RTA), ...

A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200 pgmL(-1)) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin po...

Pokeweed antiviral proteins enzymatically inactivate the 60 S subunit of eucaryotic ribosomes in cell-free preparations. Three different species of the enzyme can be isolated from spring leaves, summer leaves, and seeds of pokeweed. Sequence analyses of the NH2-terminal residues show that pokeweed antiviral protein, isolated from spring leaves and seeds, are homologous and differ in 11 of the 2...

Endocytosis and intracellular transport of ricin were studied in stable transfected HeLa cells where overexpression of wild-type (WT) or mutant dynamin is regulated by tetracycline. Overexpression of the temperature-sensitive mutant dynG273D at the nonpermissive temperature or the dynK44A mutant inhibits clathrin-dependent endocytosis (Damke, H., T. Baba, A.M. van der Blieck, and S.L. Schmid. 1...

Antibody-toxin conjugates of different compositions have been reported to have varying differential toxicities between target and non-target cells in uitro. In this report, we compare the kinetics of protein synthesis inhibition of several different types of anti-Thy 1.1-ricin hybrids. Utilizing two monoclonal antibodies which vary in affinity for the Thy 1.1 antigen by >IO3, thioether-linked ...

Intracellular activation of ricin and of the ricin A-chain (RTA) immunotoxins requires reduction of their intersubunit disulfide(s). This crucial event is likely to be catalyzed by disulfide oxidoreductases and precedes dislocation of the toxic subunit to the cytosol. We investigated the role of protein disulfide isomerase (EC 5.3.4.1, PDI), thioredoxin (Trx), and thioredoxin reductase (EC 1.8....

Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intesti...