Details:

Alternative Title:
Alcohol Clin Exp Res
Publisher's site:
http://dx.doi.org/10.1111/acer.13248
Personal Author:
Sapkota, Muna ; Kharbanda, Kusum K. ; Wyatt, Todd A.
Sapkota, Muna ; Kharbanda, Kusum K. ; Wyatt, Todd A. Less -
Description:
Background

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.

Conclusion

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


Subject:
[+]
Acetaldehyde
Adduct
Alcohol
Animals
Article
Cells, Cultured
Cigarette Smoke
Dose-Response Relationship, Drug
Humans
Interleukin-6
Macrophage
Macrophages
Malondialdehyde
Mice
Mice, Knockout
Phagocytosis
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Protein D
Rats
Scavenger Receptor A
Scavenger Receptors, Class A
Tumor Necrosis Factor-alpha

Source:
Alcohol Clin Exp Res. 40(12):2563-2572.
Pubmed ID:
27783409
Pubmed Central ID:
PMC5133169
Document Type:
Journal Article
Funding:
I01 BX000728/BX/BLRD VA/United States ; R01 AA017993/AA/NIAAA NIH HHS/United States ; U54 OH010162/OH/NIOSH CDC HHS/United States
I01 BX000728/BX/BLRD VA/United States ; R01 AA017993/AA/NIAAA NIH HHS/United States ; U54 OH010162/OH/NIOSH CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:340d16d2c765c291e7e2cb2ce326375fc1282613cdbbe67cbe9117c3ebafed0d
File Type:

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