Acute Alcohol Intoxication Impairs the Hematopoietic Precursor Cell Response to Pneumococcal Pneumonia

Authors

  • Caroline E. Raasch,

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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  • Ping Zhang,

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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  • Robert W. Siggins II,

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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  • Lynn R. LaMotte,

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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  • Steve Nelson,

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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  • Gregory J. Bagby

    1. From the Department of Physiology (CER, PZ, RWS, SN, GJB), the Alcohol Research Center (CER, PZ, RWS, SN, GJB), and the Department of Medicine, Section of Pulmonary/Critical Care Medicine (PZ, SN, GJB), School of Public Health (LRL), Louisiana State University Health Sciences Center, New Orleans, LA.
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Reprint requests: Gregory J. Bagby, PhD, Department of Physiology, LSU Health Sciences Center, New Orleans, LA 70112-1393; Tel.: 504-568-6188; Fax: 504-568-7899; E-mail: GBagby@lsuhsc.edu

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 lineagec-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 lineagec-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.

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