Alcohol misuse and smoking are risk factors for
pneumonia, yet the impact of combined cigarette
smoke and alcohol on
pneumonia remains understudied. Smokers who misuse alcohol form lung
malondialdehyde-
acetaldehyde (MAA)
protein adducts and have decreased levels of anti-MAA
secretory IgA (
sIgA).
Transforming growth factor-β (TGF-β) down-regulates
polymeric Ig receptor (pIgR) on mucosal epithelium, resulting in decreased
sIgA transcytosis to the mucosa. It is hypothesized that MAA-adducted lung
protein increases TGF-β, preventing expression of epithelial cell pIgR and decreasing
sIgA. Cigarette
smoke and alcohol co-exposure on
sIgA and TGF-β in human bronchoalveolar lavage fluid and in mice instilled with MAA-adducted
surfactant protein D (SPD-MAA) were studied herein. Human bronchial epithelial cells (HBECs) and mouse tracheal epithelial cells were treated with SPD-MAA and
sIgA and TGF-β was measured. Decreased
sIgA and increased TGF-β were observed in bronchoalveolar lavage from combined alcohol and smoking groups in humans and mice. CD204 (MAA receptor) knockout mice showed no changes in
sIgA. SPD-MAA decreased pIgR in HBECs. Conversely, SPD-MAA stimulated TGF-β release in both HBECs and mouse tracheal epithelial cells, but not in CD204 knockout mice. SPD-MAA stimulated TGF-β in alveolar macrophage cells. These data show that MAA-adducted
surfactant protein stimulates lung epithelial cell TGF-β, down-regulates pIgR, and decreases
sIgA transcytosis. These data provide a mechanism for the decreased levels of
sIgA observed in smokers who misuse alcohol.