title: Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1).
abstract: 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.
  
  
  
  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 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.
  
  
  
  Overall, the data demonstrate that SR-A1/CD204 plays an important role in SPD-MAA induced inflammation in lung.
authors.affiliation: Department of Environmental, Agricultural and Occupational Health, College of Public Health, Nebraska Medical Center, University of Nebraska Medical Center, 985910, Omaha, NE, 68198-5910, USA.
authors.forename: Muna
authors.initials: M
authors.lastname: Sapkota
authors.affiliation: Department of Internal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: DeVasure
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Nebraska Medical Center, Omaha, NE, USA.|VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.affiliation: Department of Environmental, Agricultural and Occupational Health, College of Public Health, Nebraska Medical Center, University of Nebraska Medical Center, 985910, Omaha, NE, 68198-5910, USA. twyatt@unmc.edu.|Department of Internal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, NE, USA. twyatt@unmc.edu.|VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. twyatt@unmc.edu.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
mesh_terms: D000079:Acetaldehyde / Q000506:poisoning*; D000818:Animals; D018836:Inflammation Mediators / Q000276:immunology*; D008315:Malondialdehyde / Q000506:poisoning*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000506:poisoning*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; C495140:Msr1 protein, mouse; D037663:Pulmonary Surfactant-Associated Protein D; D051117:Scavenger Receptors, Class A; D008315:Malondialdehyde; D000079:Acetaldehyde
keywords: Inflammation; Lung; MAA adduct; Scavenger receptor A