Kupffer cell stimulation in the isolated perfused rat liver triggers nuclear factor-kappaB DNA binding activity.
Activation of transcription factor NF-kappaB (electrophoretic mobility shift assay) was investigated in the isolated perfused rat liver infused with 0.5 mg of colloidal carbon/ml for 5-20 min, in relation to carbon phagocytosis and carbon-induced O(2) consumption. Experiments were carried out in control rats and in animals treated with the Kupffer cell inactivator gadolinium chloride (GdCl(3)). Carbon uptake and carbon-induced O(2) consumption by perfused livers exhibited a linear increase as a function of the perfusion time, leading to constant O(2)/carbon uptake ratios, with low (0.04-0.15%) fractional sinusoidal lactate dehydrogenase release in the 5-20 min perfusion time studied. NF-kappaB DNA binding activity showed a maximal enhancement at 10 min of carbon perfusion, a response that was sustained at a lower extent at 15 and 20 min of carbon stimulation. After 10 min of carbon infusion, NF-kappaB activation, carbon-induced O(2) consumption, and carbon uptake were diminished by 84%, 94%, and 64% by GdCl(3) treatment (P < 0.05), respectively. It is concluded that the respiratory burst of carbon-stimulated Kupffer cells triggers NF-kappaB activation in the isolated perfused liver, a response that is elicited under optimal conditions of Kupffer cell function and organ viability.
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Pamela
P
Romanque
Gladys
G
Tapia
Luis A
LA
Videla
D000818:Animals; D002244:Carbon / Q000737:chemistry; D004247:DNA / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion; D010587:Phagocytosis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016328:NF-kappa B; D002244:Carbon; D004247:DNA; D005682:Gadolinium; C038958:gadolinium chloride; D010100:Oxygen