Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia - PubMed (original) (raw)

Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia

Caroline E Raasch et al. Alcohol Clin Exp Res. 2010 Dec.

Abstract

Background: Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated.

Methods: Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae.

Results: Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection.

Conclusions: Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.

Copyright © 2010 by the Research Society on Alcoholism.

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Figures

Figure 1

Figure 1

A. Leukocytes as a percentage of total white blood cells in peripheral blood smears. Each treatment represents the mean ± SEM (n=19–35). B. Total PMN leukocyte numbers. Each treatment represents the mean ± SEM (n=12–26). Non-overlapping letters signify statistical significance (p<0.05)

Figure 2

Figure 2

Gr-1+ bronchoalveolar cells and Gr-1+BrdU+ bronchoalveolar cells recovered 6 h post i.t. challenge. Data are mean ± SEM (n = 5–7). Non-overlapping letters signify statistical significance (p < 0.05).

Figure 3

Figure 3

A. Changes in LKS cell number in the bone marrow at 24h and 48h. Data are mean ± SEM (n = 7–8). Non-overlapping letters signify statistical significance (p < 0.05). B. Changes in Sca-1 MCF in LKS cells in the bone marrow at 24h and 48h. Data are mean ± SEM (n = 7–8). Non-overlapping letters signify statistical significance (p < 0.05). A. Changes in lin−c-Kit+Sca-1− cell number in the bone marrow at 24h and 48h. Data are mean ± SEM (n = 7–8). Non-overlapping letters signify statistical significance (p < 0.05).

Figure 4

Figure 4

BrdU incorporation into bone marrow LKS cells at 24h of infection. Data are mean ± SEM (n = 7–8). Asterisks signify statistical significance from control values (p < 0.05).

Figure 5

Figure 5

A. Plasma-induced Sca-1 surface expression on lin−c-Kit+Sca-1− cells. Each treatment represents the mean ± SEM (n=15–16). Non-overlapping letters signify statistical significance (p<0.05). B. 24h post-i.t. treatment plasma levels (pg/mL) of TNF-α. Each treatment represents the mean ± SEM (n=6–10). Non-overlapping letters signify statistical significance (p<0.05).

Figure 6

Figure 6

CFU activity of bone marrow LKS and lin−c-Kit+Sca-1− cells in M3534 media. Each treatment represents the mean ± SEM (n=10–15). Non-overlapping letters signify statistical significance (p<0.05)

Figure 7

Figure 7

A. Changes in LKS cell number in the peripheral blood at 24h and 48h after pneumococcal infection with and without alcohol intoxication. Data are mean ± SEM (n = 7–8). Non-overlapping letters signify statistical significance (p < 0.05). B. Changes in Sca-1 MCF in LKS cells in the peripheral blood at 24h and 48h. Data are mean ± SEM (n = 7–8).

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