Acute alcohol intoxication inhibits the lineage- c-kit+ Sca-1+ cell response to Escherichia coli bacteremia

J Immunol. 2009 Feb 1;182(3):1568-76. doi: 10.4049/jimmunol.182.3.1568.


Alcohol abuse predisposes the host to bacterial infections. In response to bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for enhancing host defense. This study investigated the hematopoietic precursor cell response to bacteremia and how alcohol affects this response. Acute alcohol intoxication was induced in BALB/c mice 30 min before initiation of Escherichia coli bacteremia. Bacteremia caused a significant increase in the number of bone marrow lineage (lin(-))-c-kit(+)Sca-1(+) cells. Marrow lin(-)c-kit(+)Sca-1(+) cells isolated from bacteremic mice showed an increase in CFU-granulocyte/macrophage activity compared with controls. In addition to enhanced proliferation of lin(-)c-kit(+)Sca-1(+) cells as reflected by BrdU incorporation, phenotypic inversion of lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells primarily accounted for the rapid increase in marrow lin(-)c-kit(+)Sca-1(+) cells following bacteremia. Bacteremia increased plasma concentration of TNF-alpha. Culture of marrow lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells with murine rTNF-alpha for 24 h caused a dose-dependent increase in conversion of these cells to lin(-)c-kit(+)Sca-1(+) cells. Sca-1 mRNA expression by the cultured cells was also up-regulated following TNF-alpha stimulation. Acute alcohol intoxication inhibited the increase in the number of lin(-)c-kit(+)Sca-1(+) cells in the bone marrow after E. coli infection. Alcohol impeded the increase in BrdU incorporation into marrow lin(-)c-kit(+)Sca-1(+) cells in response to bacteremia. Alcohol also suppressed the plasma TNF-alpha response to bacteremia and inhibited TNF-alpha-induced phenotypic inversion of lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells in vitro. These data show that alcohol inhibits the hematopoietic precursor cell response to bacteremia, which may serve as one mechanism underlying the impaired host defense in alcohol abusers with severe bacterial infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcoholic Intoxication / immunology*
  • Alcoholic Intoxication / microbiology
  • Alcoholic Intoxication / pathology
  • Animals
  • Antigens, Ly / biosynthesis
  • Antigens, Ly / physiology
  • Bacteremia / immunology*
  • Bacteremia / microbiology
  • Bacteremia / pathology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Culture Techniques
  • Cell Differentiation / immunology
  • Cell Lineage / immunology*
  • Cytokines / blood
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Immunophenotyping
  • Immunosuppression Therapy*
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / metabolism*


  • Antigens, Ly
  • Cytokines
  • Ly6a protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins c-kit

Grant support