ALCOHOL SUPPRESSES THE STEM CELL ANTIGEN-1 RESPONSE AND GRANULOCYTE LINEAGE EXPANSION DURING BACTEREMIA
Document Type
Presentation
Start Date
22-10-2010 2:00 PM
End Date
22-10-2010 2:15 PM
Description
Enhanced Sca-1 expression by multipotent (lineage negative or lin-) hematopoietic precursors promotes myeloid lineage development in response to bacterial infection. To address whether enhanced Sca-1 expression occurs in the larger pool of downstream granulocyte lineagecommitted (granulocyte differentiation antigen-1 positive or Gr1 +) precursors and how alcohol intoxication impacts this process, E.coli bacteremia was induced in mice with or without acute alcohol intoxication. Bacteremia activated Sca-1 expression by marrow immature Gr1 10 precursors which correlated with an increase in proliferation, CFU-GM production, and expansion of this granulopoietic precursor cell pool. Alcohol suppressed Sca-1 activation and inhibited the infection-induced increases in proliferation, CFU-GM production, and expansion the of Gr1 10 cell population. Consequently, recovery of the marrow mature Gr1 hi cell population following E.coli challenge was impaired. Sca-1 was induced in sorted Gr1 +Sca1-cells by LPS-stimulated JNK activation that was also inhibited by alcohol. Furthermore, Sca-1 knockout (KO) mice failed to expand the marrow Gr1 10 cell pool and demonstrated fewer newly produced granulocytes in the circulation following E.coli challenge. Thus alcohol suppresses the Sca-1 response in granulocyte lineage-committed precursors and restricts granulocyte production during bacteremia, which may serve as a novel mechanism underlying impaired host defense in alcohol abusers.
Recommended Citation
Melvan, Nick; Siggins II, R. W.; Bagby, G. J.; and Stanford, W. L., "ALCOHOL SUPPRESSES THE STEM CELL ANTIGEN-1 RESPONSE AND GRANULOCYTE LINEAGE EXPANSION DURING BACTEREMIA" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 5.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation2/5
ALCOHOL SUPPRESSES THE STEM CELL ANTIGEN-1 RESPONSE AND GRANULOCYTE LINEAGE EXPANSION DURING BACTEREMIA
Enhanced Sca-1 expression by multipotent (lineage negative or lin-) hematopoietic precursors promotes myeloid lineage development in response to bacterial infection. To address whether enhanced Sca-1 expression occurs in the larger pool of downstream granulocyte lineagecommitted (granulocyte differentiation antigen-1 positive or Gr1 +) precursors and how alcohol intoxication impacts this process, E.coli bacteremia was induced in mice with or without acute alcohol intoxication. Bacteremia activated Sca-1 expression by marrow immature Gr1 10 precursors which correlated with an increase in proliferation, CFU-GM production, and expansion of this granulopoietic precursor cell pool. Alcohol suppressed Sca-1 activation and inhibited the infection-induced increases in proliferation, CFU-GM production, and expansion the of Gr1 10 cell population. Consequently, recovery of the marrow mature Gr1 hi cell population following E.coli challenge was impaired. Sca-1 was induced in sorted Gr1 +Sca1-cells by LPS-stimulated JNK activation that was also inhibited by alcohol. Furthermore, Sca-1 knockout (KO) mice failed to expand the marrow Gr1 10 cell pool and demonstrated fewer newly produced granulocytes in the circulation following E.coli challenge. Thus alcohol suppresses the Sca-1 response in granulocyte lineage-committed precursors and restricts granulocyte production during bacteremia, which may serve as a novel mechanism underlying impaired host defense in alcohol abusers.
Comments
See abstract book page 41