title: A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.
abstract: Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.
authors.affiliation: Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, AL, 35115, USA. noeragerb@montevallo.edu.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Noerager
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, AL, 35115, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Davis
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Caleb W
authors.initials: CW
authors.lastname: Jones
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Okafor
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Whitehead
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|UAB Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|Birmingham VA Medical Center, Birmingham, AL, 35233, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Jackson
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000626:Aminopeptidases / Q000378:metabolism; D002908:Chronic Disease; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D017572:Leukotriene A4 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D017572:Leukotriene A4; D009842:Oligopeptides; C113164:prolyl-glycyl-proline; D000171:Acrolein; D011392:Proline; D000626:Aminopeptidases; C026045:tripeptide aminopeptidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: acrolein; chronic obstructive pulmonary disease; inflammation; neutrophils