title: Malondialdehyde-Acetaldehyde-Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  In conclusion, our data demonstrate that SRA is important for MAA-adducted protein-mediated effect on macrophage functions.
authors: Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Muna
authors: M
authors: Sapkota
authors: VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Division of Gastroenterology, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Kusum K
authors: KK
authors: Kharbanda
authors: Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska.|VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Department of Internal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy University of Nebraska Medical Center, Omaha, Nebraska.
authors: Todd A
authors: TA
authors: Wyatt
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008315:Malondialdehyde / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000494:pharmacology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000079:Acetaldehyde
keywords: Adduct; Alcohol; Cigarette Smoke; Macrophage; Scavenger Receptor A