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

Details

• Personal Author:
  Kharbanda KK ; Sapkota M ; Wyatt TA
• Description:
  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-alpha) release in the macrophage cell line, RAW264.7. Results: A significant reduction in phagocytosis of zymosan particles was also observed. SPDMAA stimulated a significant dose-dependent increase in TNF-alpha and interleukin (IL)-6 release from peritoneal macrophages (PMs) of wild-type (WT) mice. But significantly less TNF-alpha and IL-6 were released from PMs of SRA -/- mice. We observed a significant reduction in phagocytosis of zymosan particles in PMs from WTmice 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-kappaB 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. [Description provided by NIOSH]
• Subjects:
  Alcoholic Beverages Aldehydes Blood Formaldehyde Immune System Laboratories Macrophages Occupational Health Safety Smokers Surface-Active Agents

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• Keywords:
  Acetaldehyde Adduct Alcohol Author Keywords: Alcohol Cigarette Smoke Cytokines Immune Reaction Laboratory Animals Macrophage Malonaldehyde Phagocytes Phagocytic Activity Proteins Scavenger Receptor A Smoking Surfactants

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• ISSN:
  0145-6008
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  40
• Issue:
  12
• NIOSHTIC Number:
  nn:20049791
• Citation:
  Alcohol Clin Exp Res 2016 Dec; 40(12):2563-2572
• Contact Point Address:
  Todd A. Wyatt, PhD, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE 68198-5910
• Email:
  twyatt@unmc.edu
• CAS Registry Number:
  Acetaldehyde (CAS RN 75-07-0) ; Malonaldehyde (CAS RN 542-78-9) ; Zymosans (CAS RN 9010-72-4)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Alcoholism: Clinical and Experimental Research
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ae5501ab942af131be0eeffbcf452695fb14c12d937007dfb89374ca8409d864e4096593065ab0bec5ec931cf39be136c5ba02ce5c10bca2d231b5b86d29d26b
• Download URL:
  https://stacks.cdc.gov/view/cdc/210421/cdc_210421_DS1.pdf
• File Type:
  [PDF - 398.47 KB ]