Acute ethanol intoxication regulates f-met-leu-phe-induced chemotaxis and superoxide release by neutrophils and Kupffer cells through modulation of the formyl peptide receptor in the rat

Abstract

This study was performed to assess alcohol-induced alterations in superoxide release and chemotaxis by Kupffer cells and blood neutrophils. Male Sprague-Dawley rats received a bolus injection of alcohol (1.75 g/Kg) followed by an intravenous infusion (250–300 mg/Kg/hr). Three or 24 hr after alcohol infusion, blood neutrophils and Kuppfer cells were isolated and assayed for f-met-leu-phe-induced chemotaxis and superoxide release, and formyl peptide receptor expression. At 3 hr post-ethanol, f-met-leu-phe-induced-chemotaxis and superoxide release by blood neutrohils were increased 2 and 3-fold, compared to saline-treated group, and were further increased at 24 hr. The expression of formyl peptide receptors was also increased from 65, 000 ± 8, 000 sites per cell to 120, 000 ± 13,000 and 200,000 ± 16,400 sites at 3 and 24 hr post-ethanol, respectively. The equilibrium dissociation constant (K D) of these receptors on neutrophils was increased at the same time interval. In contrast, alcohol infusion for 3 hr attenuated f-met-leu-phe-induced superoxide release by Kupffer cells (0.8 ± 0.25 nmol/10 6 cells), compared to saline-treated rats (3.7 ± 0.3). Chemotaxis by Kuppfer cells in response to f-met-leu-phe was also blunted by ethanol at 3 and 24 post-treatment. At 3 hr post-ethanol, the total number of binding sites and K D for f-met-leu-phe on these cells were reduced by almost 30%. The concentration and K D of high affinity binding sites and chemotactic activity of Kupffer cells were not significantly altered by ethanol at 3 hr. However, by 24 hr these were profoundly depressed.