TY - JOUR
T1 - Modification of the carbohydrate in ricin with metaperiodate and cyanoborohydride mixtures
T2 - effect on binding, uptake and toxicity to parenchymal and non-parenchymal cells of rat liver
AU - Skilleter, David N.
AU - Price, Roger J.
AU - Thorpe, Philip E.
PY - 1985/9/27
Y1 - 1985/9/27
N2 - The carbohydrate in the toxic glycoprotein ricin was chemically modified by simultaneous treatment with sodium metaperiodate and sodium cyanoborohydride. This treatment causes oxidative cleavage of the sugar residues and reduction of the aldehyde groups which are formed to primary alcohols. The modification markedly decreased the rapid removal of ricin from the blood by hepatic non-parenchymal cells with only a relatively small increase in accumulation of the toxin by parenchymal cells. Binding, uptake and toxicity of the modified ricin in primary monolayer cultures of hepatic non-parenchymalcells were all decreased to a much greater extent than in parenchymal cells. The results indicate that native ricin binds to non-parenchymal cells by a dual recognition process which involves both interaction of cell receptors with the mannose-containing oligosaccharides of the toxin and binding of ricin to galactose-containing glycoproteins and glycolipids on the cells. However, uptake and toxicity of native ricin in non-parenchymal cells appears to result principally from entry of the toxin through the mannose recognition pathway. By contrast, uptake and toxicity of the modified ricin in non-parenchymal cells, and of both ricin and the modified toxin in parenchymal cells, is expressed essentially through the galactose-recognition route.
AB - The carbohydrate in the toxic glycoprotein ricin was chemically modified by simultaneous treatment with sodium metaperiodate and sodium cyanoborohydride. This treatment causes oxidative cleavage of the sugar residues and reduction of the aldehyde groups which are formed to primary alcohols. The modification markedly decreased the rapid removal of ricin from the blood by hepatic non-parenchymal cells with only a relatively small increase in accumulation of the toxin by parenchymal cells. Binding, uptake and toxicity of the modified ricin in primary monolayer cultures of hepatic non-parenchymalcells were all decreased to a much greater extent than in parenchymal cells. The results indicate that native ricin binds to non-parenchymal cells by a dual recognition process which involves both interaction of cell receptors with the mannose-containing oligosaccharides of the toxin and binding of ricin to galactose-containing glycoproteins and glycolipids on the cells. However, uptake and toxicity of native ricin in non-parenchymal cells appears to result principally from entry of the toxin through the mannose recognition pathway. By contrast, uptake and toxicity of the modified ricin in non-parenchymal cells, and of both ricin and the modified toxin in parenchymal cells, is expressed essentially through the galactose-recognition route.
KW - (Hepatic parenchymal, non-parenchymal cells)
KW - Chemical modification
KW - Ricin accumulation
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=0021997092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021997092&partnerID=8YFLogxK
U2 - 10.1016/0304-4165(85)90287-9
DO - 10.1016/0304-4165(85)90287-9
M3 - Article
C2 - 2994746
AN - SCOPUS:0021997092
SN - 0304-4165
VL - 842
SP - 12
EP - 21
JO - BBA - General Subjects
JF - BBA - General Subjects
IS - 1
ER -