HLTH 210 Chapter Notes - Chapter 16: Alveolar Macrophage, Immunodeficiency, Glutathione
5 May 2018
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Guidot reading - “alcoholism causes alveolar macrophage zinc deficiency and immune
dysfunction”
● Conclusion - evidence that alcohol abuse is associated with significant zinc deficiency
and immune dysfunction within the alveolar space and suggest that dietary
supplementation with zinc and glutathione precursors could enhance airway innate
immunity and decrease the risk for pneumonia or lung injury in these vulnerable
individuals
● Lifetime prevalence of alcohol abuse in US is 18% and over half of population in US
older than 12 yo consumes alcohol
● Alcohol abuse is the 3rd leading cause of preventable death in US
● Consequences of alcoholism span multiple organ systems: heart, liver, brain, skeletal
muscle
● Chronic alcohol ingestion causes cellular dysfunction and oxidative stress through the
following mechanisms
○ Shown in glutathione level decrease within alveolar space and impaired
phagocytosis in alveolar macrophages
○ Also decreased signaling of granulocyte-macrophage colony-stimulating factor
(GM-CSF) mediates alveolar macrophage immune deficiency
○ Also zinc deficiency drives oxidative stress and impaired GM-CSF signaling,
linked to development of pneumonia
● Used healthy alcoholics in study
● Results
○ Alveolar macrophages isolated from subjects with an AUD had lower intracellular
zinc levels
○ In contrast, serum zinc levels didn’t differ between alcoholic and control subjects
and did not correlate with alveolar macrophage zinc levels
○ Alveolar macrophages from alcoholic subjects had decreased bacterial
phagocytic capacity
○ The cell surface expression of the signaling subunit of the GM-CSF receptor was
decreased in the alveolar macrophages of alcoholic subjects
○ Treating isolated alveolar macrophages with zinc and/or GSH in vitro increased
intracellular zinc levels and phagocytic capacity, and these salutary effects were
most pronounced in response to combination treatment
● Animal models have been instrumental in characterizing what we have termed the
“alcoholic lung phenotype”
● There are no currently available treatments to mitigate the adverse effects of chronic
alcohol use on the lung
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Document Summary
Guidot reading - alcoholism causes alveolar macrophage zinc deficiency and immune dysfunction . Lifetime prevalence of alcohol abuse in us is 18% and over half of population in us older than 12 yo consumes alcohol. Alcohol abuse is the 3rd leading cause of preventable death in us. Consequences of alcoholism span multiple organ systems: heart, liver, brain, skeletal muscle. Chronic alcohol ingestion causes cellular dysfunction and oxidative stress through the following mechanisms. Shown in glutathione level decrease within alveolar space and impaired phagocytosis in alveolar macrophages. Also decreased signaling of granulocyte-macrophage colony-stimulating factor (gm-csf) mediates alveolar macrophage immune deficiency. Also zinc deficiency drives oxidative stress and impaired gm-csf signaling, linked to development of pneumonia. Alveolar macrophages isolated from subjects with an aud had lower intracellular zinc levels. In contrast, serum zinc levels didn"t differ between alcoholic and control subjects and did not correlate with alveolar macrophage zinc levels. Alveolar macrophages from alcoholic subjects had decreased bacterial phagocytic capacity.
