title: Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia.
abstract: BACKGROUND
  Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated.
  
  
  METHODS
  Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae.
  
  
  RESULTS
  Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection.
  
  
  CONCLUSIONS
  Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112-1393, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Raasch
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Robert W
authors.initials: RW
authors.lastname: Siggins
authors.forename: Lynn R
authors.initials: LR
authors.lastname: LaMotte
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced / Q000150:complications; D000435:Alcoholic Intoxication / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins