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.
Bautista
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AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Elliott
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KE
D000818:Animals; D001665:Binding Sites; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D018000:Receptors, Peptide / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D000431:Ethanol; D009240:N-Formylmethionine Leucyl-Phenylalanine