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Malondialdehyde–Acetaldehyde‐Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A
Author(s) -
Sapkota Muna,
Kharbanda Kusum K.,
Wyatt Todd A.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13248
Subject(s) - scavenger receptor , chemistry , malondialdehyde , surfactant protein a , cytokine , alveolar macrophage , tumor necrosis factor alpha , zymosan , macrophage , microbiology and biotechnology , biochemistry , pharmacology , endocrinology , biology , immunology , pulmonary surfactant , oxidative stress , cholesterol , lipoprotein , in vitro
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 ; CD 204) 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 ‐ κ B 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.