Acetaldehyde-serum protein adducts inhibit interleukin-2 secretion in concanavalin A-stimulated murine splenocytes: a potential common pathway for ethanol-induced immunomodulation.
Variable immunobiological changes occur with alcohol consumption. Previous studies have shown that acetaldehyde forms stable adducts with serum proteins, including albumin. These adducts are elevated in persons and animals consuming ethanol. We examined the effect of serum protein-acetaldehyde adducts formed with fetal bovine serum (FBS) on concanavalin A-stimulated murine splenocytes. Interleukin-2 (IL-2) secretion and IL-2 receptor (IL-2R) expression were determined as a function of the effect of the acetaldehyde-protein adduct(s). FBS was incubated with acetaldehyde (500, 100, 50, 25, 10, and 0 microM) for 1 hr at 37 degrees C. Excess acetaldehyde was removed by ultrafiltration using a 500 molecular weight cut-off membrane in 3 volumes. Free as well as bound acetaldehyde was quantified using fluorigenic HPLC before and after incubation. Recovered acetaldehyde correlated with the amount added (r2 = 0.996). Splenocytes were cultured for 48 hr in complete medium containing 5% acetaldehyde-treated and 5% untreated FBS with 4 micrograms/ml concanavalin A. Although cell viability was unchanged, acetaldehyde-treated FBS mixed with native FBS decreased IL-2 secretion in a dose-dependent manner. The percentage of cells expressing IL-2R was reduced only at the highest acetaldehyde-FBS dose. Therefore, immunological effects ascribed to ethanol may result in part from the toxic properties of acetaldehyde-protein adducts on IL-2 secretion.
Braun
K P
KP
Sansum Medical Research Foundation, Santa Barbara, California 93105, USA.
Pearce
R B
RB
Peterson
C M
CM
D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001798:Blood Proteins / Q000187:drug effects*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003208:Concanavalin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D007108:Immune Tolerance / Q000187:drug effects; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000494:pharmacology
D001798:Blood Proteins; D007376:Interleukin-2; D003208:Concanavalin A; D012710:Serum Albumin, Bovine; D000431:Ethanol; D000079:Acetaldehyde