Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1)

Details

• Alternative Title:
  Respir Res
• Personal Author:
  Sapkota, Muna ; DeVasure, Jane M. ; Kharbanda, Kusum K. ; Wyatt, Todd A.
• Description:
  Background
  
  Co-exposure to cigarette smoke and alcohol leads to the generation of high concentrations of acetaldehyde and malondialdehyde in the lung. These aldehydes being highly electrophilic in nature react with biologically relevant proteins such as surfactant protein D (SPD) through a Schiff base reaction to generate SPD adducted malondialdehyde-acetaldehyde adduct (SPD-MAA) in mouse lung. SPD-MAA results in an increase in lung pro-inflammatory chemokine, keratinocyte chemoattractant (KC), and the recruitment of lung lavage neutrophils. Previous in vitro studies in bronchial epithelial cells and macrophages show that scavenger receptor A (SR-A1/CD204) is a major receptor for SPD-MAA. No studies have yet examined the in vivo role of SR-A1 in MAA-mediated lung inflammation. Therefore, we hypothesize that in the absence of SR-A1, MAA-induced inflammation in the lung is reduced or diminished.
  
  Methods
  
  To test this hypothesis, C57BL/6 WT and SR-A1 KO mice were nasally instilled with 50 μg/mL of SPD-MAA for 3 weeks (wks). After 3 weeks, bronchoalveolar lavage (BAL) fluid was collected and assayed for a total cell count, a differential cell count and CXCL1 (KC) chemokine. Lung tissue sections were stained with hematoxylin and eosin (H&E) and antibodies to MAA adduct.
  
  Results
  
  Results showed that BAL cellularity and influx of neutrophils were decreased in SR-A1 KO mice as compared to WT following repetitive SPD-MAA exposure. MAA adduct staining in the lung epithelium was decreased in SR-A1 KO mice. In comparison to WT, no increase in CXCL1 was observed in BAL fluid from SR-A1 KO mice over time.
  
  Conclusions
  
  Overall, the data demonstrate that SR-A1/CD204 plays an important role in SPD-MAA induced inflammation in lung.
  
  
• Subjects:
  Inflammation Lung MAA Adduct Research Scavenger Receptor A
• Source:
  Respir Res. 18.
• Pubmed ID:
  28193223
• Pubmed Central ID:
  PMC5307820
• 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
• Volume:
  18
• NIOSHTIC Number:
  nn:20049378
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e7aaedd167d399726ea98eeaf5873e9e2e282abb504ba7e4fa44caa539c58ed02b2de54af57d4208b18abb966dc4c336c569bcce1cb5d454a272bbf7166b53e6
• Download URL:
  https://stacks.cdc.gov/view/cdc/44612/cdc_44612_DS1.pdf
• File Type:
  [PDF - 1.45 MB ]