ACUTE ETHANOL INTOXICATION REGULATES F-MET-LEU-PHE-INDUCED CHEMOTAXISAND 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 supe roxide 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 superox ide release, and formyl peptide receptor expression. At 3 hr post-etha nol, f-met-leu-phe-induced-chemotaxis and superoxide release by blood neutrohils were increased 2 and 3-fold, compared to saline-treated gro up, and were further increased at 24 hr. The expression of formyl pept ide 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 interva l. In contrast, alcohol infusion for 3 hr attenuated f-met-leu-phe-ind uced superoxide release by Kupffer cells (0.8 +/- 0.25 nmol/l0(6) cell s), compared to saline-treated rats (3.7 +/- 0.3). Chemotaxis by Kupff er 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 bind ing sites and K-D for f-met-leu-phe on these cells were reduced by alm ost 30%. The concentration and K-D of high affinity binding sites and chemotactic activity of Kupffer cells and were not significantly alter ed by ethanol at 3 hr. However, by 24 hr these were profoundly depress ed.