Impairment of Hematopoietic Precursor Cell Activation during the Granulopoietic Response to Bacteremia in Mice with Chronic-Plus-Binge Alcohol Administration.

Impairment of Hematopoietic Precursor Cell Activation during the Granulopoietic Response to Bacteremia in Mice with Chronic-Plus-Binge Alcohol Administration.

Shi Xin; Lin Yuan-Ping; Gao Bin; Zhang Ping

Infection and immunity

2017

2017-11

Alcohol abuse impairs immune defense. To study the effect of chronic-plus-binge alcohol exposure on the granulopoietic response, acute alcohol intoxication (intraperitoneal injection of 5 g alcohol/kg body weight) was introduced to mice chronically fed on the Lieber-DeCarli low-fat liquid alcohol diet for 5 weeks. Bacteremia was induced by intravenous injection of Escherichia coli Bacteremia caused a remarkable increase in marrow lin(-) c-kit(+) Sca-1(+) cells. Activation of cell proliferation supported the increase in marrow lin(-) c-kit(+) Sca-1(+) cells. Alcohol administration inhibited this activation of lin(-) c-kit(+) Sca-1(+) cells. The bone marrow of pair-fed control mice receiving intraperitoneal saline stored a large number of mature granulocytes expressing a high level of Gr1 (Gr1(hi) cells). The proportion of Gr1(hi) cells and the total number of Gr1(+) cells were markedly reduced in the bone marrow, along with an increase in the ratio of Gr1(+) granulocytes in peripheral white blood cells following bacteremia. E. coli infection stimulated proliferation of granulopoietic precursor cells, resulting in a marked increase in the ratio of immature Gr1(lo) cells in the bone marrow. Alcohol administration itself triggered marrow release of Gr1(+) cells, resulting in reduction of the marrow granulocyte reserve with an elevation of granulocytes in the circulation. Alcohol also impaired activation of granulopoietic precursor proliferation following bacteremia. Alcohol disrupted lipopolysaccharide (LPS)-TLR4-ERK1/2-cyclin D1 signaling and inhibited upregulation of Sca-1 and C/EBPbeta expression by lineage-negative marrow cells in response to bacteremia. These results indicate that chronic-plus-binge alcohol exposure inhibits the granulopoietic response by disrupting key cell signaling for hematopoietic precursor cell activation and commitment to granulocyte lineage development.

*Alcohol; *bacteremia; *cell signaling; *granulocytes; *granulopoietic response; *stem cells; Animal; Animals; Antigens; Bacteremia/genetics/*immunology/pathology; Binge Drinking/genetics/*immunology/pathology; Bone Marrow Cells/drug effects/immunology/pathology; CCAAT-Enhancer-Binding Protein-beta/genetics/immunology; Cyclin D1/genetics/immunology; Disease Models; Escherichia coli Infections/genetics/*immunology/pathology; Escherichia coli/growth & development/immunology; Ethanol/*pharmacology; Gene Expression Regulation/*drug effects/immunology; Granulocytes/drug effects/immunology/pathology; Hematopoiesis/*drug effects/genetics/immunology; Inbred BALB C; Ly/genetics/immunology; Male; Membrane Proteins/genetics/immunology; Mice; Mitogen-Activated Protein Kinase 1/genetics/immunology; Mitogen-Activated Protein Kinase 3/genetics/immunology; Nucleotidyltransferases/deficiency/genetics/immunology; Proto-Oncogene Proteins c-kit/genetics/immunology; Signal Transduction/*drug effects/immunology; Toll-Like Receptor 4/genetics/immunology

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

11

85