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B activation after intratracheal
endotoxin
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville 37232-2650; and Department of Medicine, Department of Veterans Affairs, Nashville, Tennessee 37212
We examined the relationship between nuclear
factor (NF)-
B DNA binding activity, cytokine gene
expression, and neutrophilic alveolitis in rats after intratracheal
(IT) instillation of endotoxin [lipopolysaccharide (LPS)].
NF-B activation in lung tissue mirrored neutrophilic alveolitis
after IT LPS instillation, with NF-B activation and neutrophilic
influx beginning 2 h after IT LPS doses of 0.01 mg/kg or greater. In
lung lavage fluid cells, however, transient NF-B
activation was present in alveolar macrophages by 15 min after IT LPS
instillation, followed by a second peak of NF-B activation
corresponding to the onset on neutrophilic alveolitis. For cytokines
thought to be NF-B dependent, two different patterns of mRNA
expression were found. Interleukin (IL)-1
, IL-1
, and tumor
necrosis factor- showed increased mRNA by 30 min after IT LPS
instillation, but IL-6- and cytokine-induced neutrophil chemoattractant
mRNAs were not substantially increased until 2 h after IT LPS
instillation. Therefore, IT LPS causes differential NF-B activation
in air space cells and lung tissue, which likely determines production
of key cytokines and directs the evolution of neutrophilic alveolitis.
nuclear factor-B; lung; neutrophil; inflammation; chemokine; macrophage
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