Malondialdehyde-Acetaldehyde Adduct Formation Decreases Immunoglobulin A Transport across Airway Epithelium in Smokers Who Abuse Alcohol

Todd A. Wyatt, Kristi J. Warren, Tanner J. Wetzel, Troy Suwondo, Gage P. Rensch, Jane M. DeVasure, Deanna D. Mosley, Kusum K. Kharbanda, Geoffrey M. Thiele, Ellen L. Burnham, Kristina L. Bailey, Samantha M. Yeligar

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1732-1742
Number of pages11
JournalAmerican Journal of Pathology
Volume191
Issue number10
DOIs
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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