Changes in the Superoxide Production and Other Macrophage
Functions Could Be Related to the Mortality of Mice with
Endotoxin-Induced Oxidative Stress
V. M. VÍCTOR, M. DE LA FUENTE
Department of Animal Physiology, Faculty of Biological
Sciences, Complutense University, Madrid, Spain
Received
January 10, 2002
Accepted May 22, 2002
Summary
Free radicals and proinflammatory cytokines from phagocytes have
been implicated in the pathogenesis of endotoxic shock, a
disease with high mortality caused by Gram-negative bacterial
endotoxin. In the present study, male BALB/c and Swiss mice
received intraperitoneally lipopolysaccharide (LPS) at 100 mg/kg
and 150 mg/kg, respectively, that led to a lethal endotoxic
shock (100 % of mortality before 30 h). Swiss mice injected with
100 mg/kg, that did not show lethal endotoxic shock, were also
studied. Peritoneal macrophages were obtained from animals at 2,
4, 12 or 24 h after injection of LPS or saline (control)
solutions. Superoxide anion and tumor necrosis factor (TNFα)
production were determined in these cells as well as other
functions such as adherence capacity, chemotaxis and
phagocytosis. The increase in superoxide anion production after
endotoxin injection was higher in cells from mice with lethal
shock than in those with non-lethal shock. However, the
enhancement of TNFα production was similar in all cases,
although in Swiss mice the highest levels of TNFα were observed
at 1.5 h after endotoxin injection, while in BALB/c mice they
occurred at 2 h after LPS injection. This oxidative stress was
also revealed by the other functions analyzed, since adherence
to substrate and phagocytosis were stimulated and chemotaxis was
decreased after endotoxin injection as compared to controls, the
differences being even more significant in animals with lethal
shock. These data suggest that these changes, mainly the
increased production of free radicals even more than the TNFα
release, could be involved in mouse mortality caused by LPS.
Key
words
Immune function • Macrophage • Mice • Oxidative Stress •
Superoxide anion
Reprint
requests
Dr. Mónica De la Fuente, Departamento de Biología Animal II (Fisiología
Animal). Facultad de Ciencias Biológicas. Universidad
Complutense. Av. Complutense s/n, 28040 Madrid, Spain. Fax:
+34-91-3944935, e-mail:
mondelaf@bio.ucm.es
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