Alcohol exposure impairs myeloid dendritic cell function in rhesus macaques.
BACKGROUND
Alcohol intoxication suppresses both the innate and adaptive immunities. Dendritic cells (DCs) are the major cell type bridging the innate and acquired immune responses. At the present time, the effects of alcohol on DC development in hematopoietic tissues and the functional activities of DCs are incompletely elucidated. This study investigated the impact of chronic alcohol exposure on the alteration of hematopoietic precursor cell and DC populations in the bone marrow and peripheral blood of rhesus macaques.


METHODS
Rhesus macaques were administered alcohol or isocaloric sucrose daily for a period of 3 months through surgically implanted gastric catheters. Peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were isolated for flow cytometric analysis after 3 months. Monocytes were cultured with human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml) in the absence and presence of alcohol (50 mM). On day 6 of the culture, a cocktail of stimulants including IL-1beta (18 ng), IL-6 (1800 U), TNF-alpha (18 ng), and PGE(2) (1.8 microg) were added to the designated wells for transformation of immature dendritic cells (iDCs) to mature myeloid DCs. The cells were analyzed on day 8 by flow cytometry for expression of DC costimulatory molecule expression.


RESULTS
EtOH-treated animals had significantly lower numbers of myeloid DCs (lineage-HLA-DR+CD11c+CD123-) in both the PBMCs and BMCs compared to controls (5,654 +/- 1,273/10(6) vs. 2,353 +/- 660/10(6) PBMCs and 503 +/- 34 vs. 195 +/- 44/10(6) BMCs). Under culture conditions, the number of lineage-HLA-DR+CD83+ cells was low in control wells (0.38 +/- 0.08%). Alcohol inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in iDC wells (2.30 +/- 0.79% vs. 5.73 +/- 1.40%). Alcohol also inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in mature DC wells (1.23 +/- 0.15% vs. 4.13 +/- 0.62%).


CONCLUSIONS
Chronic EtOH decreases the bone marrow and circulating pools of myeloid DCs. Additionally, EtOH suppresses costimulatory molecule CD83 expression during DC transformation, which may attenuate the ability of DCs to initiate T-cell expansion.
Siggins
Robert W
RW
Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112-1393, USA.
Bagby
Gregory J
GJ
Molina
Patricia
P
Dufour
Jason
J
Nelson
Steve
S
Zhang
Ping
P
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003713:Dendritic Cells / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects
D002492:Central Nervous System Depressants; D008565:Membrane Proteins; D000431:Ethanol