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

Muna Sapkota, Jane M. DeVasure, Kusum Kharbanda, Todd A Wyatt

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Abstract

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.

Original languageEnglish (US)
Article number36
JournalRespiratory Research
Volume18
Issue number1
DOIs
StatePublished - Feb 13 2017

Fingerprint

Scavenger Receptors
Acetaldehyde
Malondialdehyde
Surface-Active Agents
Pneumonia
Pulmonary Surfactant-Associated Protein D
Proteins
Lung
Chemotactic Factors
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Keratinocytes
Chemokines
Neutrophils
Cell Count
Schiff Bases
Hematoxylin
Eosine Yellowish-(YS)
Aldehydes
Smoke

Keywords

  • Inflammation
  • Lung
  • MAA adduct
  • Scavenger receptor A

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

@article{da7c34e14dd84a88b8c5d73c947f0a8f,
title = "Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1)",
abstract = "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.",
keywords = "Inflammation, Lung, MAA adduct, Scavenger receptor A",
author = "Muna Sapkota and DeVasure, {Jane M.} and Kusum Kharbanda and Wyatt, {Todd A}",
year = "2017",
month = "2",
day = "13",
doi = "10.1186/s12931-017-0517-x",
language = "English (US)",
volume = "18",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1)

AU - Sapkota, Muna

AU - DeVasure, Jane M.

AU - Kharbanda, Kusum

AU - Wyatt, Todd A

PY - 2017/2/13

Y1 - 2017/2/13

N2 - 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.

AB - 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.

KW - Inflammation

KW - Lung

KW - MAA adduct

KW - Scavenger receptor A

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U2 - 10.1186/s12931-017-0517-x

DO - 10.1186/s12931-017-0517-x

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