Acute Alcohol Intoxication Inhibits Stem Cell Antigen‐1 Expression by Gr1+ Myeloid Lineage Committed Precursor Cells during Bacteremia

Abstract

Hematopoietic precursor cells preferentially commit toward the granulocyte lineage during bacterial infection. Our previous studies have shown that alcohol intoxication impairs stem cell antigen‐1 (Sca1) expression by lineage negative hematopoietic precursor cells during bacterial infection, a key component of the granulopoietic response. It remains unknown whether alcohol affects the Sca1 response in myeloid lineage committed (Gr1+) cells. Thirty minutes after intraperitoneal injection of alcohol (5g EtOH/kg), male Balb/c mice received an intravenous injection of E. coli and BrdU. Bacteremia increased the number of Gr1lo and Gr1hi cells expressing Sca1. Increased Sca1 expression during bactermia was accompanied by greater BrdU incorporation and CFU activity in Gr1lo cells compared to controls. In culture, 12hrs of LPS exposure stimulated the expression of Sca1 by sorted Gr1+Sca1‐ cells. Alcohol intoxication suppressed the Sca1 response, BrdU incorporation, and CFU activity of Gr1lo cells. These data show that alcohol suppresses Sca1 expression in cells committed to myeloid lineage development during bacteremia. Inhibiting the Sca1 response in downstream myeloid cells may serve as a mechanism of alcohol induced myelosuppression and thereby impair host defense against bacterial infection. NIH NRSA AA09803, AA017494, and AA07577.