4 years ago

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

Gao B, Zhang P, Lin YP, Shi X
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 5g 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 amount of mature granulocytes expressing a high level of Gr1 (Gr1hi cells). The proportion of Gr1hi cells and total number of Gr1+ cells 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 Gr1lo cells in the bone marrow. Alcohol administration itself triggered marrow release of Gr1+ cells resulting in reduction of marrow granulocyte reserve with an elevation of granulocytes in the circulation. Alcohol also impaired activation of granulopoietic precursor proliferation following bacteremia. Alcohol disrupted LPS/TLR4- ERK1/2-cyclin D1 signaling and inhibited up-regulation of Sca-1 and C/EBPβ expression by lineage negative marrow cells in response to bacteremia. These results indicate that chronic-plus-binge alcohol exposure inhibits the granulopoietic response through disrupting key cell signaling for hematopoietic precursor cell activation and their commitment to granulocyte lineage development.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28784931

DOI: PubMed:28784931

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