title: Dysregulation of myelopoiesis by chronic alcohol administration during early SIV infection of rhesus macaques.
abstract: 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.
authors.affiliation: 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.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Siggins
authors.forename: Patricia
authors.initials: P
authors.lastname: Molina
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.forename: Jason
authors.initials: J
authors.lastname: Dufour
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: LeCapitaine
authors.forename: Cullen
authors.initials: C
authors.lastname: Walsh
authors.forename: David A
authors.initials: DA
authors.lastname: Welsh
mesh_terms: D000437:Alcoholism / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D008253:Macaca mulatta; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D038042:Myelopoiesis / Q000187:drug effects*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000503:physiopathology*
chemical_list: D000431:Ethanol
keywords: Alcohol; Bone Marrow; Hematopoiesis; Immune Cells; Simian Immunodeficiency Virus