A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation
- PDF / 633,029 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 87 Downloads / 177 Views
A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation Brett D. Noerager,1,7 Xin Xu,2 Virginia A. Davis,1 Caleb W. Jones,2,3 Svetlana Okafor,3 Alicia Whitehead,3 J. Edwin Blalock,2,4 and Patricia L. Jackson2,4,5,6
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 metalloproteinase9 (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. KEY WORDS: acrolein; neutrophils; inflammation; chronic obstructive pulmonary disease.
INTRODUCTION Neutrophils (polymorphonuclear leukocytes, PMNs) are an integral component of the inflammatory process in many pulmonary diseases such as chronic obstructive pulmonary disease (COPD) [1, 2] and cystic fibrosis (CF) [3, 4]. While the etiology of these two diseases is quite different, the behavior of the PMNs at the site of inflammation in the lungs is similar. Once attracted to the area of inflammation, neutrophils respond by releasing toxic reactive species such as superoxide and nitric oxide [5], as well as 1
Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, AL 35115, USA 2 Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA 3 Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA 4 UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA 5 UAB Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA 6 Birmingham VA Medical Center, Birmingham, AL 35233, USA 7 To whom correspondence should be addressed at Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, AL 35115, USA. E-mail: [email protected]
activating the enzymes myeloperoxidase (MPO), matrix metalloproteinases (MMPs), and human neutrophil elastase (HNE). In response to a microbial infection, these toxic products destroy the pathogen. However, in a chronic inflammatory condition such as is present in COPD and CF, thes
Data Loading...
