Agonist-stimulated Ca2+ response in neutrophils from patients with primary alcoholism and alcoholized healthy subjects

The sensitivity of the inositol phosphate (IP)/Ca2+-second messenger generating system was assessed in neutrophils from healthy volunteers before and after ingestion of approximately 1%o ethanol for 2 h. In addition, isolated neutrophils from healthy subjects were incubated with ethanol in vitro. Furthermore, the sensitivity of the IP/Ca2+ system was evaluated in neutrophils from alcoholic patients in the state of active drinking, and after 2-3 weeks and 6 months of abstinence. EC50 values of the concentration-response curves obtained by agonist stimulation with formyl-methionyl-leucylphenylalanine (fMLP) of the intracellular Ca2+ accumulation were determined as an indicator of the sensitivity of the system. Ingestion of ethanol by healthy volunteers (both in the ex vivo and in vitro experiments) induced a rightward shift of the concentration-response curve (higher EC50 values) in neutrophils, indicating a reduced sensitivity to agonist stimulation evoked by ethanol. The sensitivity of the Ca2+ response in neutrophils from alcoholic patients decreased intraindividually after a period of 2-3 weeks of abstinence (higher EC50 values) and was at this time also significantly lower compared to a group of matched healthy controls In contrast, the maximal Ca2+ release induced by a saturating concentration of fMLP was increased after 2-3 weeks of abstinence, both intraindividually and in comparison to healthy controls. These alterations of the EC50 values and the maximal Ca2+ response were normalized after 6 months of abstinence. It is concluded that ethanol attenuates the sensitivity of the IP/Ca2+ system in neutrophils in healthy subjects. In neutrophils from alcoholic subjects complex alterations appear to persist up to several weeks, which are only normalized after a prolonged period of abstinence.