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Alcohol Suppresses Stem Cell Antigen‐1‐Associated Myeloid Precursor Proliferation During Bacteremia
Author(s) -
Melvan John Nicholas,
Siggins Robert W.,
Porretta Connie,
Nelson Steve,
Bagby Gregory J.,
Zhang Ping
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1043.3
Subject(s) - mapk/erk pathway , myeloid , flow cytometry , cell growth , stem cell , cell , cell cycle , biology , cancer research , immunology , chemistry , microbiology and biotechnology , kinase , biochemistry
Our previous studies have shown that enhancement of stem cell antigen‐1 (Sca1) expression by myeloid precursors is associated with increased granulocyte production during bacterial infection. Using phosphospecific flow cytometry, we studied the role of Sca1 in promoting ERK‐dependent myeloid precursor proliferation and the affects of alcohol on this response. Thirty minutes after i.p. injection of 20% EtOH (5g/kg), mice were i.v. challenged with 5 x 10 7 E.coli for 8 h. Marrow ERK activation and the number of Sca1+pERK+ cells increased during infection. ERK was activated in LKS‐ and Gr1 lo but not Gr1 hi cells. Gr1 lo Sca1+ cells had greater ERK and cell cycle activity than Gr1 lo Sca1‐ cells. Sca‐1 expression correlated with ERK activation in Gr1 lo cells during infection. Alcohol suppressed ERK activation in marrow cells and the increase in number of Sca1+pERK+ cells during infection. Alcohol‐induced ERK suppression also occurred in LKS‐, Gr1 lo , and Gr1 hi cells during infection. Enhanced ERK and cell cycle activity of Gr1 lo Sca‐1+ cells was suppressed by alcohol. Sca1KO mice failed to activate ERK in total marrow and Gr1 lo cells during infection. Thus enhanced Sca1 expression may promote ERK‐mediated proliferation of myeloid precursors during infection. Alcohol suppresses this response. NIH AA017494 , AA019676 , AA09803, AA07577, AA019586.