Human neutrophil functions are inhibited in vitro by clinically relevant ethanol concentrations.
Neutrophils [polymorphonuclear neutrophils (PMNs)] play a pivotal role in host defense in man. These defenses may be compromised, however, in alcohol users and abusers. We therefore evaluated the effect of ethanol levels (12.5 to 500 mg/dl), on key functions of human PMNs-chemotaxis and production of reactive oxygen species-and on changes in cytosolic-free calcium ([Ca2+]i), a pivotal intracellular mechanism of PMN activation. Ethanol significantly inhibited chemotaxis as evaluated by formyl-methionyl-leucyl-phenylalanine (fMLP)-induced upregulation of surface adhesion molecules (CD11b). fMLP-induced PMN elongation was only inhibited by a very high ethanol concentration of 500 mg/dl. Production of reactive oxygen species by normal PMNs was assessed by either chemiluminescence (CL) for hypochlorous acid or ferricytochrome c reduction (FCR) for superoxide anions. For PMN stimulated by fMLP, ethanol inhibited CL but not FCR. For PMNs activated by phorbol myristate acetate, ethanol inhibited both CL and FCR. Ethanol did not alter baseline [Ca2+]i, as assessed by videomicroscopy using the Ca(2+)-sensing fluorescent dye Fura-2-AM, but did significantly potentiate the increase in peak [Ca2+]i levels that occurs in response to stimulation by fMLP. Calcium channel blockers attenuated ethanol's inhibition of CL. Thus, acute in vitro ethanol, at clinically relevant concentrations, can inhibit several critical aspects of PMN functions. But, in PMNs, unlike neural cells, these inhibitory effects do not seem to be mediated by decreases in Ca2+ influx or in [Ca2+]i.
Patel
M
M
Department of Medicine, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
Keshavarzian
A
A
Kottapalli
V
V
Badie
B
B
Winship
D
D
Fields
J Z
JZ
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D066298:In Vitro Techniques; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017382:Reactive Oxygen Species; D000431:Ethanol; D002118:Calcium