Ethanol affects leukotriene generation and leukotriene-induced functional responses in human polymorphonuclear granulocytes.
Since ethanol has been shown to inhibit the inflammatory response, we evaluated whether ethanol affected generation of leukotrienes in polymorphonuclear granulocytes (PMN) in vitro. Using the calcium ionophore A23187 as stimulus, the leukotriene B4 (LTB4) and leukotriene C4 (LTC4) generation were dose-dependently impaired by ethanol. No significant difference in the levels of the omega-oxidized metabolites was observed. However, the total LTB4 production (LTB4 plus omega-oxidized metabolites) was significantly decreased in the samples treated with ethanol. Furthermore, ethanol also modulated LTB4-induced functional responses. PMN aggregation, oxidative metabolism and elastase release were all inhibited in the presence of 1% ethanol (to 74 +/- 15%, 50 +/- 4% and 57 +/- 3% of controls, respectively). However, ethanol had no effect on intracellular calcium mobilization or on the change of the PMN membrane potential induced by either LTB4 or A23187. Thus, a possible mechanism for the reduced functional PMN responses in the presence of ethanol might be impaired generation of leukotrienes, but it is conceivable that ethanol impairs also other steps of the stimulus response coupling since the LTB4-induced functional responses were inhibited.
Nilsson
E
E
Department of Medicine, Karolinska Institute at Stockholm Söder Hospital, Sweden.
Edenius
C
C
Lindgren
J A
JA
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002449:Cell Aggregation / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000502:physiology*; D017997:Leukotriene C4 / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D012016:Reference Values; D013481:Superoxides / Q000378:metabolism
D007476:Ionophores; D013481:Superoxides; D007975:Leukotriene B4; D017997:Leukotriene C4; D000001:Calcimycin; D000431:Ethanol; D015759:Ionomycin; D002118:Calcium