Role of tumor necrosis factor and interferon gamma in endotoxin-induced E-selectin expression.
Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), potent inflammatory cytokines, are released by macrophages during endotoxin shock. However, the contribution of these cytokines to endotoxin-induced inflammation has not been defined. The expression of E-selectin, measured using the dual radiolabeled monoclonal antibody (mAb) technique, was monitored in different tissues of endotoxin-challenged wild-type and IFN-gamma-deficient mice receiving a mAb to TNF-alpha (TN3). A significant elevation in E-selectin expression occurred in all tissues of wild-type mice challenged with endotoxin. Injection of TN3 in wild-type mice significantly attenuated the endotoxin-induced up-regulation of E-selectin in all tissues (p < .05) except the pancreas. The level of reduction in endotoxin-induced E-selectin expression ranged between 30% in the stomach to 60% in the small intestine. E-selectin expression in endotoxin-challenged, IFN-gamma-deficient mice was significantly reduced in the small and large intestines, when compared with endotoxin-challenged wild-type mice. Although IFN-gamma deficiency had no effect on E-selectin expression in other tissues, administration of TN3 to endotoxin-challenged, IFN-gamma-deficient mice significantly reduced E-selectin expression to levels observed in endotoxin-challenged, wild-type mice that received TN3. These findings indicate that TNF-alpha is essential for achievement of maximal E-selectin expression in most vascular beds during endotoxemia, whereas the contribution of IFN-gamma is largely confined to the small intestine.
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
M J
MJ
Eppihimer
J
J
Russell
R
R
Langley
M
M
Gerritsen
D N
DN
Granger
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004926:Escherichia coli; D005753:Gastric Mucosa / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007420:Intestine, Large / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma