Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells

John P Berger, Samantha M. Simet, Jane M. DeVasure, Jessica A. Boten, Jenea M. Sweeter, Kusum K. Kharbanda, Joseph H. Sisson, Todd A. Wyatt

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Co-exposure to cigarette smoke and ethanol generates malondialdehyde and acetaldehyde, which can subsequently lead to the formation of aldehyde-adducted proteins. We have previously shown that exposure of bronchial epithelial cells to malondialdehyde-acetaldehyde (MAA) adducted protein increases protein kinase C (PKC) activity and proinflammatory cytokine release. A specific ligand to scavenger receptor A (SRA), fucoidan, blocks this effect. We hypothesized that MAA-adducted protein binds to bronchial epithelial cells via SRA. Human bronchial epithelial cells (BEAS-2B) were exposed to MAA-adducted protein (either bovine serum albumin [BSA-MAA] or surfactant protein D [SPD-MAA]) and SRA examined using confocal microscopy, fluorescent activated cell sorting (FACS), and immunoprecipitation. Differentiated mouse tracheal epithelial cells (MTEC) cultured by air-liquid interface were assayed for MAA-stimulated PKC activity and keratinocyte-derived chemokine (KC) release. Specific cell surface membrane dye co-localized with upregulated SRA after exposure to MAA for 3-7 min and subsided by 20 min. Likewise, MAA-adducted protein co-localized to SRA from 3 to 7 min with a subsequent internalization of MAA by 10 min. These results were confirmed using FACS analysis and revealed a reduced mean fluorescence of SRA after 3 min. Furthermore, increased amounts of MAA-adducted protein could be detected by Western blot in immunoprecipitated SRA samples after 3 min treatment with MAA. MAA stimulated PKCε-mediated KC release in wild type, but not SRA knockout mice. These data demonstrate that aldehyde-adducted proteins in the lungs rapidly bind to SRA and internalize this receptor prior to the MAA-adducted protein stimulation of PKC-dependent inflammatory cytokine release in airway epithelium.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalAlcohol
Volume48
Issue number5
DOIs
StatePublished - Aug 2014

Keywords

  • Acetaldehyde
  • Airway epithelial
  • Lung
  • Malondialdehyde
  • Scavenger receptor

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    Berger, J. P., Simet, S. M., DeVasure, J. M., Boten, J. A., Sweeter, J. M., Kharbanda, K. K., Sisson, J. H., & Wyatt, T. A. (2014). Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells. Alcohol, 48(5), 493-500. https://doi.org/10.1016/j.alcohol.2014.02.005