Interactions of Shiga-like toxin with human peripheral blood monocytes.
The cytotoxic effect of Shiga-like toxin (Stx; produced by certain Escherichia coli strains) plays a central role in typical hemolytic uremic syndrome (HUS). It damages the renal endothelium by inhibiting the cellular protein synthesis. Also, the monocyte has a specific receptor for Stx but is not sensitive for the cytotoxic effect. In this work, monocytes were studied as a potential transporter for Stx to the renal endothelium. Coincubation of isolated human monocytes loaded with Stx and target cells (vero cells and human umbilical vascular endothelial cells) were performed. Transfer was determined by measuring the protein synthesis of target cells and by flow cytometry. Furthermore, the effect of a temperature shift on loaded monocytes was investigated. Stx-loaded monocytes reduced the protein synthesis of target cells. After adding an antibody against Stx, incomplete recovery occurred. Also, adding only the supernatant of coincubation was followed by protein synthesis inhibition. Stx detached from its receptor on the monocyte after a change in temperature, and no release was detected without this temperature shift. Although the monocyte plays an important role in the pathogenesis of HUS, it has no role in the transfer of Stx.
Geelen
Joyce M
JM
Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. j.geelen@cukz.umcn.nl
van der Velden
Thea J A M
TJ
van den Heuvel
Lambertus P W J
LP
Monnens
Leo A H
LA
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism*; D022621:Shiga Toxin / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D014709:Vero Cells
D022621:Shiga Toxin