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Cell death by apoptosis mediates several important physiologic
and pathologic and processes and appeares to be intrinsically
programmed. In the study, we found that intraperitoneal
injection of Gram-negative bacteria (Escherichia coli,
Klebsiella pneumoniae, Pseudomonas aeruginosa) induces atrophy
of the thymus in mice. The thymus weight, cell number, and
viability began to decrease 3 h after E. coli injection, the
reduction reached maximum on 72 h. The thymocytes death were
also associated with DNA fragment of ~200 b.p. in ladder form.
the kinetic study on histopathology clearly revealed the
process of thymocytes death and thymic atrophy. Flow cytometric
analysis showed that CD4+CD8+ tymocytes decreased
predominantly, but was accompanied by an increase of CD4+CD8-
cells. Furthermore, Gram-negative sepsis induced apoptosis of
the thymus in LPS-responder mice (C3H/HeN) as well as in LPS-
nonresponder mice (C3H/HeJ). Interestingly, Gram-positive
bacteria (Streptococcus pneumoniae) also caused apoptosis of
the thymus in LPS-nonresponder mice. These data suggest that
not only endotoxin but also some other components derived from
bacteria can elicit apoptosis of the thymocytes in mice.
Furthermore, anti-TNF.alpha. Ab complete inhibit Gram-negative
sepsis-induced apoptosis.Gram- negative E. coli induced serum
TNF.alpha. peak at 1 h, while Gram-positive S. pneumoniae at
6-9 h. Moreover, mouse TNF.alpha. alsoenhanced thymocyte
apoptosis in in vitro culture thymocyte induced apoptosis. Our
results further showed pretreatment with actinomycin D,
cycloheximide and IVIG could inhibit the E.coli- induced
thymocyte apoptosis. This suggests that TNF.alpha. is a common
mediator involved in Gram-negative or Gram-positive bacteria
induced apoptosis of the thymocytes in mice and protein or RNA
synthesis were required for this apoptosis.
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