Malondialdehyde-Acetaldehyde Adduct Formation Decreases Immunoglobulin a Transport Across Airway Epithelium in Smokers Who Abuse Alcohol

Details

• Personal Author:
  Bailey KL ; Burnham EL ; DeVasure JM ; Kharbanda KK ; Mosley DD ; Rensch GP ; Suwondo T ; Thiele GM ; Warren KJ ; Wetzel TJ ; Wyatt TA ; Yeligar SM
• Description:
  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-ß 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-ß 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-ß 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. [Description provided by NIOSH]
• Subjects:
  Alcoholic Beverages Blood Lung Macrophages Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Smokers Tobacco Products

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• Keywords:
  Alcoholic Beverages Alveolar Cells Cigarette Smoking Pneumonia Proteins Respiratory System Disorders
• ISSN:
  0002-9440
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Georgia ; Nebraska ; OSHA Region 4 ; OSHA Region 7 ; OSHA Region 8 ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  191
• Issue:
  10
• NIOSHTIC Number:
  nn:20063799
• Citation:
  Am J Pathol 2021 Oct; 191(10):1732-1742
• Contact Point Address:
  Todd A. Wyatt, Ph.D., University of Nebraska, 985910 Nebraska MedicalCenter, Omaha, NE 68198-5910
• Email:
  twyatt@unmc.edu
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  The American Journal of Pathology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:17965ff96b14c0b9df983f4e29d7bfc9511bcb83eca7923dbd0cf1ff2456c949d79447db267b5ae12b06afd2562630ad9dd2f983b1651c0c52ea1657ce436e2b
• Download URL:
  https://stacks.cdc.gov/view/cdc/222352/cdc_222352_DS1.pdf
• File Type:
  [PDF - 830.45 KB ]