PMID- 24942272 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20211021 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 38 IP - 7 DP - 2014 Jul TI - Dysregulation of myelopoiesis by chronic alcohol administration during early SIV infection of rhesus macaques. PG - 1993-2000 LID - 10.1111/acer.12433 [doi] AB - BACKGROUND: Chronic alcohol intoxication suppresses immune function and increases osteoporosis risk suggesting bone-tissue cytotoxicity. Human immunodeficiency virus infection leads to similar impairments. This study investigated the effects of chronic alcohol administration during the early stage of simian immunodeficiency virus (SIV) infection on hematopoietic stem and progenitor cells (HSPCs) and their differentiated progeny in the bone marrow and peripheral blood of rhesus macaques. METHODS: Rhesus macaques were administered alcohol or sucrose daily for a period of 3 months prior to intrarectal inoculation with 250 TCID50 of SIVmac251 . Bone marrow aspirates and blood samples were taken prior to and 2 weeks after SIV infection. Bone marrow cells (BMCs) were assessed using flow cytometric phenotyping for upstream HSPCs and for differentiated cells of the monocyte-granulocyte lineages. Likewise, cells were quantitated in peripheral blood. RESULTS: Of the bone marrow HSPCs, only the common lymphoid progenitor (CLP) was altered by alcohol administration pre-SIV (38 +/- 9.4/10(6) BMCs vs. 226 +/- 64.1/10(6) BMCs, sucrose vs. alcohol). Post-SIV, the frequency of CLPs in the bone marrow of alcohol-administered macaques decreased compared with the sucrose-administered macaques (107 +/- 47.6/10(6) BMCs vs. 43 +/- 16.3/10(6) BMCs). However, marrow mature cells of the monocyte lineage, specifically macrophages and osteoclast progenitors, were increased by both chronic alcohol administration and SIV infection (287% and 662%, respectively). As expected, mature cells such as granulocytes (polymorphonuclear cells), B cells, and CD4+ T cells in the peripheral blood were decreased by SIV infection (37 to 62% decline from preinfection), but not affected after 3 months of chronic alcohol administration. CONCLUSIONS: Chronic alcohol administration disrupts myelomonocytic development in the bone marrow during the early period of SIV infection promoting macrophage and osteoclast lineages. We predict this shift in CLP:macrophage/osteoclast balance creates an environment that favors bone resorption and immunosuppression. CI - Copyright (c) 2014 by the Research Society on Alcoholism. FAU - Siggins, Robert W AU - Siggins RW AD - Comprehensive Alcohol Research Center , Louisiana State University Health Sciences Center, New Orleans, Louisiana; Department of Physiology , Louisiana State University Health Sciences Center, New Orleans, Louisiana. FAU - Molina, Patricia AU - Molina P FAU - Zhang, Ping AU - Zhang P FAU - Bagby, Gregory J AU - Bagby GJ FAU - Nelson, Steve AU - Nelson S FAU - Dufour, Jason AU - Dufour J FAU - LeCapitaine, Nicole J AU - LeCapitaine NJ FAU - Walsh, Cullen AU - Walsh C FAU - Welsh, David A AU - Welsh DA LA - eng GR - P60 AA009803/AA/NIAAA NIH HHS/United States GR - AA021097/AA/NIAAA NIH HHS/United States GR - T35 DK093428/DK/NIDDK NIH HHS/United States GR - T35 AA021097/AA/NIAAA NIH HHS/United States GR - K99 AA020312/AA/NIAAA NIH HHS/United States GR - R25 OD010515/OD/NIH HHS/United States GR - R00 AA020312/AA/NIAAA NIH HHS/United States GR - AA020312/AA/NIAAA NIH HHS/United States GR - P51 OD011104/OD/NIH HHS/United States GR - T35 HL105350/HL/NHLBI NIH HHS/United States GR - R25 AA021304/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 - 20140618 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 3K9958V90M (Ethanol) SB - IM MH - Alcoholism/blood/complications/*pathology/*physiopathology MH - Animals MH - Bone Marrow/drug effects MH - Ethanol/*administration & dosage/*adverse effects MH - Hematopoietic Stem Cells/cytology/drug effects MH - Macaca mulatta MH - Myeloid Cells/cytology/drug effects MH - Myelopoiesis/*drug effects MH - Simian Acquired Immunodeficiency Syndrome/blood/*physiopathology PMC - PMC4138983 MID - NIHMS582318 OTO - NOTNLM OT - Alcohol OT - Bone Marrow OT - Hematopoiesis OT - Immune Cells OT - Simian Immunodeficiency Virus EDAT- 2014/06/20 06:00 MHDA- 2015/04/15 06:00 PMCR- 2015/07/01 CRDT- 2014/06/20 06:00 PHST- 2013/12/20 00:00 [received] PHST- 2014/03/17 00:00 [accepted] PHST- 2014/06/20 06:00 [entrez] PHST- 2014/06/20 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1111/acer.12433 [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2014 Jul;38(7):1993-2000. doi: 10.1111/acer.12433. Epub 2014 Jun 18.