Malondialdehyde-Acetaldehyde-Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A

Alcohol Clin Exp Res. 2016 Dec;40(12):2563-2572. doi: 10.1111/acer.13248. Epub 2016 Oct 26.

Abstract

Background: Reactive aldehydes such as acetaldehyde and malondialdehyde generated as a result of alcohol metabolism and cigarette smoke exposure lead to the formation of malondialdehyde-acetaldehyde-adducted proteins (MAA adducts). These aldehydes can adduct to different proteins such as bovine serum albumin and surfactant protein A or surfactant protein D (SPD). Macrophages play an important role in innate immunity, but the effect of MAA adducts on macrophage function has not yet been examined. Because macrophage scavenger receptor A (SRA; CD204) mediates the uptake of modified proteins, we hypothesized that the effects of MAA-modified proteins on macrophage function are primarily mediated through SRA.

Methods: We tested this hypothesis by exposing SPD-MAA to macrophages and measuring functions. SPD-MAA treatment significantly stimulated pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) release in the macrophage cell line, RAW 264.7.

Results: A significant reduction in phagocytosis of zymosan particles was also observed. SPD-MAA stimulated a significant dose-dependent increase in TNF-α and interleukin (IL)-6 release from peritoneal macrophages (PMs) of wild-type (WT) mice. But significantly less TNF-α and IL-6 were released from PMs of SRA-/- mice. We observed a significant reduction in phagocytosis of zymosan particles in PMs from WT mice treated with SPD-MAA. No further SPD-MAA-induced reduction was seen in PMs from SRA-/- mice. SPD-MAA treatment significantly increased SRA mRNA expression, but had no effect on surface receptor protein expression. Protein kinase C alpha inhibitor and NF-κB inhibitor significantly reduced pro-inflammatory cytokine release in response to SPD-MAA.

Conclusions: In conclusion, our data demonstrate that SRA is important for MAA-adducted protein-mediated effect on macrophage functions.

Keywords: Adduct; Alcohol; Cigarette Smoke; Macrophage; Scavenger Receptor A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetaldehyde / chemistry*
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-6 / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Malondialdehyde / chemistry*
  • Mice
  • Mice, Knockout
  • Phagocytosis / drug effects
  • Pulmonary Surfactant-Associated Protein A / chemistry
  • Pulmonary Surfactant-Associated Protein A / pharmacology*
  • Pulmonary Surfactant-Associated Protein D / chemistry
  • Pulmonary Surfactant-Associated Protein D / pharmacology*
  • Rats
  • Scavenger Receptors, Class A / biosynthesis
  • Scavenger Receptors, Class A / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Scavenger Receptors, Class A
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Acetaldehyde