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 beta (TGFβ) downregulates polymeric Ig receptor (pIgR) on mucosal epithelium, resulting in decreased sIgA transcytosis to the mucosa. It is hypothesized that MAA-adducted lung protein increases TGFβ, preventing expression of epithelial cell pIgR and decreasing sIgA. Cigarette smoke and alcohol co-exposure on sIgA and TGFβ in human bronchoalveolar lavage (BAL) fluid and in mice instilled with MAA-adducted surfactant protein D (SPD-MAA) were studied herein. Human (HBEC) and mouse (MTEC) lung epithelial cells were treated with SPD-MAA and sIgA and TGFβ measured. Decreased sIgA and increased TGFβ were observed in BAL 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 HBEC. Conversely, SPD-MAA stimulated TGFβ release in both HBEC and MTEC, but not in CD204 knockout mice. SPD-MAA stimulated TGFβ in alveolar macrophage cells. These data demonstrate that MAA-adducted surfactant protein stimulates lung epithelial cell TGFβ, downregulates pIgR, and decreases sIgA transcytosis. These data provide a mechanism for the decreased levels of sIgA observed in smokers who misuse alcohol.
Copyright © 2021. Published by Elsevier Inc.