Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leucocytes through a common receptor.
The main cause of acute renal failure in children is HUS (haemolytic uraemic 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 bloodstream and are targeted to cerebral and renal endothelium triggering HUS. PMN (polymorphonuclear leucocytes) seem to be involved in Stx delivery through an unidentified membrane receptor (Kd=10⁻⁸ M; 2×10⁵ binding sites) which does not allow internalization. Some experts in the field have defined the Stx-PMN interaction as non-specific and of little biological significance. In the present study, we show that the A chain of ricin, the well-known plant RIP (ribosome-inactivating protein), interacts with PMN (Kd=10⁻⁹ M; 2×10⁵ binding sites) competing for the same receptor that recognizes Stx, whereas diphtheria toxin and several agonists of TLRs (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 leucocytes. Moreover, two single-chain RIPs (gelonin and saporin S6) had 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.
Arfilli
Valentina
V
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Carnicelli
Domenica
D
Rocchi
Laura
L
Ricci
Francesca
F
Pagliaro
Pasqualepaolo
P
Tazzari
Pier Luigi
PL
Brigotti
Maurizio
M
D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D004167:Diphtheria Toxin / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type / Q000819:agonists / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000819:agonists / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000819:agonists / Q000378:metabolism*; D012276:Ricin / Q000378:metabolism* / Q000494:pharmacology; D022622:Shiga Toxin 1 / Q000378:metabolism* / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism
D004167:Diphtheria Toxin; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D022622:Shiga Toxin 1; D051193:Toll-Like Receptors; D012276:Ricin