Malondialdehyde-Acetaldehyde (MAA) Adducted Surfactant Protein Alters Macrophage Functions through Scavenger Receptor A
Published Date:Oct 26 2016
Source:Alcohol Clin Exp Res. 40(12):2563-2572.
Pubmed Central ID:PMC5133169
Funding:I01 BX000728/BX/BLRD VA/United States
R01 AA017993/AA/NIAAA NIH HHS/United States
U54 OH010162/OH/NIOSH CDC HHS/United States
Reactive aldehydes like 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 album (BSA) and surfactant proteins A or D (SPA, 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 and Results
We tested this hypothesis by exposing SPD-MAA to macrophages and measuring functions. SPD-MAA treatment significantly stimulated pro-inflammatory cytokine TNF-α release in the macrophage cell line, RAW 264.7. A significant reduction in phagocytosis of zymosan particles was also observed. SPD-MAA stimulated a significant dose-dependent increase in TNF-α and IL-6 release from peritoneal macrophages of WT mice. But a significantly less TNF-α and IL-6 were released from peritoneal macrophages of SRA−/− mice. We observed a significant reduction in phagocytosis of zymosan particles in peritoneal macrophages from WT mice treated with SPD-MAA. No further SPD-MAA-induced reduction was seen in peritoneal macrophages form 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.
In conclusion, our data demonstrate that SRA is important for MAA-adducted protein-mediated effect on macrophage functions.
Supporting Files:No Additional Files
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