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.

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 Kupffer 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 neutrophils 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 (KD) 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 Kupffer 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 KD for f-met-leu-phe on these cells were reduced by almost 30%. The concentration and KD 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.