title: Suppression of the stem cell antigen-1 response and granulocyte lineage expansion by alcohol during septicemia.
abstract: OBJECTIVE
  Granulocytopenia frequently occurs in alcohol abusers with severe bacterial infection, which strongly correlates with poor clinical outcome. Knowledge of the molecular mechanisms underlying the granulopoietic response to bacterial infection remains limited. This study investigated the involvement of stem cell antigen-1 expression by granulocyte lineage-committed progenitors in the granulopoietic response to septicemia and how alcohol affected this response.
  
  
  METHODS
  : Laboratory investigation.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male Balb/c mice.
  
  
  METHODS
  Thirty mins after intraperitoneal injection of alcohol (20% ethanol in saline at 5 g of ethanol/kg) or saline, mice received an intravenous Escherichia coli challenge.
  
  
  RESULTS
  E. coli septicemia activated stem cell antigen-1 expression by marrow immature granulocyte differentiation antigen-1 precursors which correlated with an increase in proliferation, granulocyte macrophage colony-forming unit production, and expansion of this granulopoietic precursor cell pool. Acute alcohol treatment suppressed stem cell antigen-1 activation and inhibited the infection-induced increases in proliferation, granulocyte macrophage colony-forming unit production, and expansion the of immature granulocyte differentiation antigen-1 precursor cell population. Consequently, recovery of the marrow mature granulocyte differentiation antigen-1 cell population after E. coli challenge was impaired. Stem cell antigen-1 was induced in sorted granulocyte differentiation antigen-1, stem cell antigen-1' cells by lipopolysaccharide-stimulated C-Jun kinase activation that was also inhibited by alcohol. Furthermore, stem cell antigen-1 knockout mice failed to expand the marrow immature granulocyte differentiation antigen-1 cell pool and demonstrated fewer newly produced granulocytes in the circulation after the E. coli challenge.
  
  
  CONCLUSIONS
  Alcohol suppresses the stem cell antigen-1 response in granulocyte lineage-committed precursors and restricts granulocyte production during septicemia, which may serve as a novel mechanism underlying impaired host defense in alcohol abusers.
authors: Departments of Physiology, Section of Pulmonary/Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors: John N
authors: JN
authors: Melvan
authors: Robert W
authors: RW
authors: Siggins
authors: Gregory J
authors: GJ
authors: Bagby
authors: William L
authors: WL
authors: Stanford
authors: David A
authors: DA
authors: Welsh
authors: Steve
authors: S
authors: Nelson
authors: Ping
authors: P
authors: Zhang
references: Crit Care Med. 2007 Feb;35(2):345-50
references: 17205003
references: FEMS Immunol Med Microbiol. 2004 Mar 8;40(2):147-53
references: 14987733
references: J Emerg Med. 2010 Jan;38(1):12-7
references: 18547772
references: Leukemia. 2004 Nov;18(11):1760-8
references: 15457182
references: Natl Vital Stat Rep. 2008 Apr 24;56(10):1-120
references: 18512336
references: J Immunol. 2011 Apr 1;186(7):4306-13
references: 21357267
references: J Exp Med. 2005 Jun 6;201(11):1771-80
references: 15939792
references: J Clin Invest. 1973 Jun;52(6):1410-4
references: 4703227
references: J Biol Chem. 2004 Mar 19;279(12):10883-91
references: 14699155
references: J Immunol. 2009 Feb 1;182(3):1568-76
references: 19155505
references: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5840-5
references: 12732718
references: Proc Soc Exp Biol Med. 1984 Feb;175(2):219-25
references: 6607476
references: Stem Cells. 2010 Jan;28(1):122-6
references: 19890981
references: J Exp Med. 1997 Aug 29;186(5):705-17
references: 9271586
references: Immunol Cell Biol. 1995 Aug;73(4):277-96
references: 7493764
references: Shock. 2005 Apr;23(4):344-52
references: 15803058
references: Exp Hematol. 2005 Jul;33(7):836-43
references: 15963860
references: Blood. 2008 Jan 1;111(1):42-9
references: 17928531
references: J Cell Physiol. 1981 Oct;109(1):17-24
references: 7035470
references: Science. 2003 Jun 6;300(5625):1524-5
references: 12791976
references: Curr Clin Top Infect Dis. 1997;17:291-315
references: 9189671
references: Stem Cells. 2008 Jul;26(7):1778-86
references: 18483422
references: Nature. 2009 Apr 16;458(7240):904-8
references: 19212321
references: Alcohol Clin Exp Res. 1998 Dec;22(9):1927-42
references: 9884135
references: Cytokine. 2010 Aug;51(2):127-31
references: 20483637
references: Nature. 2008 May 22;453(7194):544-7
references: 18497826
references: JAMA. 1986 Sep 19;256(11):1474-9
references: 3747066
references: Immunity. 2006 Jun;24(6):801-812
references: 16782035
references: J Clin Invest. 1967 Dec;46(12):1943-53
references: 6073999
references: Blood. 2005 Feb 15;105(4):1785-96
references: 15514007
references: N Engl J Med. 1982 Sep 30;307(14):845-9
references: 7110259
references: Blood. 2003 Jan 15;101(2):517-23
references: 12393491
references: Alcohol Clin Exp Res. 2006 Aug;30(8):1436-44
references: 16899048
references: Nat Cell Biol. 2002 May;4(5):E131-6
references: 11988758
references: J Immunol. 2006 Jun 15;176(12):7628-35
references: 16751410
references: Am J Physiol. 1996 Oct;271(4 Pt 1):L587-92
references: 8897906
references: Stem Cells. 2008 Apr;26(4):1009-16
references: 18258722
references: Nat Rev Immunol. 2010 Mar;10(3):201-9
references: 20182459
references: J Immunol. 2007 Feb 1;178(3):1243-9
references: 17237368
references: Stem Cells. 2002;20(6):514-21
references: 12456959
references: Am Rev Respir Dis. 1985 Oct;132(4):757-60
references: 4051312
references: Blood. 2002 Aug 1;100(3):854-61
references: 12130495
references: Blood. 1992 Dec 15;80(12):3044-50
references: 1281687