Shiga toxin induces superoxide production in polymorphonuclear cells with subsequent impairment of phagocytosis and responsiveness to phorbol esters.
The role of inflammatory cells in the pathogenesis of hemolytic-uremic syndrome induced by Shiga toxin (Stx)-producing Escherichia coli remains unclear. The hypothesis that Stx has direct effects on polymorphonuclear cell (PMN) viability and function was examined by measuring apoptosis, necrosis, phagocytosis, and spontaneous and phorbol myristate acetate (PMA)-stimulated production of reactive oxygen intermediates. PMN from 6 healthy persons were exposed to medium, Stx1 (0.01-100 ng/mL), or heat-inactivated Stx1 or Stx1 B subunit (100 ng/mL). Stx1 induced a prominent dose-dependent respiratory burst from PMN at doses as low as 0.01 ng/mL; they were less responsive to PMA stimulation and had reduced ability for phagocytosis. This dysfunction was not due to cell death, as the magnitude of apoptosis and necrosis of PMN treated with Stx1 (100 ng/mL) for 20 h was identical to that of medium control. These results suggest that Stx has direct effects on PMN that could contribute to tissue injury early in the disease.
King
A J
AJ
Division of Nephrology, New England Medical Center, Boston, MA 02111, USA.
Sundaram
S
S
Cendoroglo
M
M
Acheson
D W
DW
Keusch
G T
GT
D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D010703:Phorbol Esters / Q000633:toxicity; D022603:Shiga Toxins; D013481:Superoxides / Q000378:metabolism*
D001427:Bacterial Toxins; D002273:Carcinogens; D015815:Cell Adhesion Molecules; D010703:Phorbol Esters; D022603:Shiga Toxins; D013481:Superoxides