Induction of thymic apoptosis by Shiga toxin from Escherichia coli O157:H7 in vivo and in vitro.
It is not known how Shiga toxins (Stxs), which are major virulence factors of enterohemorrhagic Escherichia coli, can affect the host immune system. We investigated the effect of Stx2 on murine thymic cells in vivo and in vitro. After intraperitoneal administration of Stx2, the body weight of mice (BW) and the organ index of thymocytes (OIT) gradually decreased from day 1 to day 4. Apoptosis of thymocytes, assessed by TUNEL staining, and DNA fragmentation assay, was marked on day 3 and day 4. Decrease in BW and OIT due to Stx2 was antagonized by the simultaneous administration of murine anti-Stx2 IgG antibody with Stx2. In vitro administration of Stx2 also induced apoptosis of cultured thymocytes on day 3 and day 4 in a dose-dependent fashion. These results showed that Stx2 directly caused apoptosis of thymocytes in vivo and in vitro. Our findings imply that StA2 may be intimately related to pathogenesis of E. coli O157:H7 infection, by causing apoptosis of thymus.
Iwata
M
M
Department of Gastroenterology, Osaka City University Medical School, Osaka, Japan. iwata@med.osaka-cu.ac.jp
Hotta
H
H
Higuchi
K
K
Nishiuchi
Y
Y
Fujiwara
Y
Y
Arakawa
T
T
Yano
I
I
Kobayashi
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019453:Escherichia coli O157; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D022641:Shiga Toxin 2 / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D022641:Shiga Toxin 2