Lack of dendritic cell maturation by the plant toxin ricin.
Several bacterial toxins either promote or inhibit the maturation of human monocyte-derived DC. Since the potent plant toxin ricin exploits the same cell entry pathway used by these bacterial toxins and shares identical catalytic activity with some of them, we have studied the capacity of ricin to induce DC maturation in vitro. Here, we show that in contrast to the bacterial proteins, ricin neither induces DC maturation nor interferes with LPS-induced DC maturation. There is no correlation between the absence of DC maturation and ricin dysfunction. Indeed, some of the ricin variants retain significant ribotoxicity and catalytic activity. We have extended these observations to ebulin-1, suggesting that this may be a general characteristic of plant-derived cytotoxic ribosome-inactivating toxins. The human immune system may therefore have evolved to recognize and rapidly respond to the bacterial proteins, whilst being less responsive to the equivalent plant cytotoxins. Understanding the effect of ricin on professional APC may provide insights into the generation of an anti-ricin vaccine and into the use of inactivated ricin A chains as delivery vectors as part of a vaccination protocol.
Smith
Daniel C
DC
Molecular Cell Biology Group, Department of Biological Sciences, University of Warwick, Coventry, GB.
Salio
Mariolina
M
Lord
J Michael
JM
Roberts
Lynne M
LM
Cerundolo
Vincenzo
V
D002454:Cell Differentiation / Q000187:drug effects*; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009336:Necrosis; D010940:Plant Proteins / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000235:genetics / Q000494:pharmacology*
D002619:Chemical Warfare Agents; D008070:Lipopolysaccharides; D010940:Plant Proteins; D020033:Protein Isoforms; D054790:Ribosome Inactivating Proteins, Type 2; C107391:ebulin r protein, Sambucus ebulus; D012276:Ricin