PMID- 19485975 OWN - NLM STAT- MEDLINE DCOM- 20091116 LR - 20211020 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 33 IP - 9 DP - 2009 Sep TI - Alcohol exposure impairs myeloid dendritic cell function in rhesus macaques. PG - 1524-31 LID - 10.1111/j.1530-0277.2009.00980.x [doi] AB - 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. FAU - Siggins, Robert W AU - Siggins RW AD - Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112-1393, USA. FAU - Bagby, Gregory J AU - Bagby GJ FAU - Molina, Patricia AU - Molina P FAU - Dufour, Jason AU - Dufour J FAU - Nelson, Steve AU - Nelson S FAU - Zhang, Ping AU - Zhang P LA - eng GR - P60 AA009803/AA/NIAAA NIH HHS/United States GR - AA07577/AA/NIAAA NIH HHS/United States GR - R01 AA013543/AA/NIAAA NIH HHS/United States GR - R01 AA013543-04S1/AA/NIAAA NIH HHS/United States GR - R01 AA011290/AA/NIAAA NIH HHS/United States GR - P60 AA009803-16S1/AA/NIAAA NIH HHS/United States GR - AA11290/AA/NIAAA NIH HHS/United States GR - R01 AA011290-15/AA/NIAAA NIH HHS/United States GR - T32 AA007577/AA/NIAAA NIH HHS/United States GR - T32 AA007577-09/AA/NIAAA NIH HHS/United States GR - R37 AA011290/AA/NIAAA NIH HHS/United States GR - AA09803/AA/NIAAA NIH HHS/United States GR - P50 AA009803/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090526 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 0 (Central Nervous System Depressants) RN - 0 (Membrane Proteins) RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Bone Marrow Cells/*drug effects MH - Cells, Cultured MH - Central Nervous System Depressants/*toxicity MH - Dendritic Cells/*drug effects MH - Ethanol/*toxicity MH - Flow Cytometry MH - Hematopoietic Stem Cells/*drug effects MH - Macaca mulatta MH - Membrane Proteins/biosynthesis MH - Monocytes/drug effects PMC - PMC2948236 MID - NIHMS235407 EDAT- 2009/06/03 09:00 MHDA- 2009/11/17 06:00 PMCR- 2010/10/01 CRDT- 2009/06/03 09:00 PHST- 2009/06/03 09:00 [entrez] PHST- 2009/06/03 09:00 [pubmed] PHST- 2009/11/17 06:00 [medline] PHST- 2010/10/01 00:00 [pmc-release] AID - ACER980 [pii] AID - 10.1111/j.1530-0277.2009.00980.x [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2009 Sep;33(9):1524-31. doi: 10.1111/j.1530-0277.2009.00980.x. Epub 2009 May 26.