title: Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells.
abstract: Co-exposure to cigarette smoke and ethanol generates malondialdehyde and acetaldehyde, which can subsequently lead to the formation of aldehyde-adducted proteins. We have previously shown that exposure of bronchial epithelial cells to malondialdehyde-acetaldehyde (MAA) adducted protein increases protein kinase C (PKC) activity and proinflammatory cytokine release. A specific ligand to scavenger receptor A (SRA), fucoidan, blocks this effect. We hypothesized that MAA-adducted protein binds to bronchial epithelial cells via SRA. Human bronchial epithelial cells (BEAS-2B) were exposed to MAA-adducted protein (either bovine serum albumin [BSA-MAA] or surfactant protein D [SPD-MAA]) and SRA examined using confocal microscopy, fluorescent activated cell sorting (FACS), and immunoprecipitation. Differentiated mouse tracheal epithelial cells (MTEC) cultured by air-liquid interface were assayed for MAA-stimulated PKC activity and keratinocyte-derived chemokine (KC) release. Specific cell surface membrane dye co-localized with upregulated SRA after exposure to MAA for 3-7 min and subsided by 20 min. Likewise, MAA-adducted protein co-localized to SRA from 3 to 7 min with a subsequent internalization of MAA by 10 min. These results were confirmed using FACS analysis and revealed a reduced mean fluorescence of SRA after 3 min. Furthermore, increased amounts of MAA-adducted protein could be detected by Western blot in immunoprecipitated SRA samples after 3 min treatment with MAA. MAA stimulated PKCε-mediated KC release in wild type, but not SRA knockout mice. These data demonstrate that aldehyde-adducted proteins in the lungs rapidly bind to SRA and internalize this receptor prior to the MAA-adducted protein stimulation of PKC-dependent inflammatory cytokine release in airway epithelium.
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Berger
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Simet
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: DeVasure
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Boten
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Jenea M
authors.initials: JM
authors.lastname: Sweeter
authors.affiliation: Research Service, VA Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE 68105, USA; Gastroenterology and Hepatology Division, Department of Internal Medicine, 988090 Nebraska Medical Center, Omaha, NE 68198-8090, USA.
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.affiliation: Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Sisson
authors.affiliation: Research Service, VA Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE 68105, USA; Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA; Department of Environmental, Agricultural, and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198-5910, USA. Electronic address: twyatt@unmc.edu.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D051117:Scavenger Receptors, Class A; C074302:keratinocyte-derived chemokines; D008315:Malondialdehyde; D011493:Protein Kinase C; D000079:Acetaldehyde
keywords: Acetaldehyde; Airway epithelial; Lung; Malondialdehyde; Scavenger receptor