Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leukocytes through a common receptor
Résumé
The main cause of acute renal failure in children is HUS (hemolytic uremic syndrome), a consequence of intestinal infections with Escherichia coli strains producing Stx (Shiga toxins). Stx released in the gut by the non-invasive bacteria reach the blood stream and are targeted to cerebral and renal endothelium triggering HUS. PMN (polymorphonuclear leukocytes) seem involved in Stx delivery through an unidentified membrane receptor (Kd = 10-8 M; 2 x 105 binding sites) which does not allow internalization. Some experts in the field have defined the interaction Stx/PMN as non-specific and of little biological significance. Here, we show that the A chain of ricin, the well known plant RIP (ribosome-inactivating protein), interacts with PMN (Kd = 10-9 M; 2 x 105 binding sites) competing for the same receptor that recognizes Stx, whereas diphtheria toxin and several agonists of Toll-like receptors or the mannose-receptor were ineffective. No toxic effects of ricin A chain on PMN were observed, as assessed by measuring protein synthesis and the rate of spontaneous apoptosis of leukocytes. Moreover, two single-chain RIPs (gelonin, saporin S6) showed the same competing effect. Thus, RIPs and Stx1 share structural similarities, the same enzymatic activity and a common receptor on PMN. These observations reveal that the Stx/PMN interaction is specific confirming that PMN recognize molecular patterns common to different foreign molecules.
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