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A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation

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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.

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Acknowledgments

JEB is funded through NIH (HL07783, HL090999, and HL087824). PLJ is supported by Cystic Fibrosis Foundation R464-CR11 “Research Development Program-Component II” and NIH/NIDDK P30 DKO72482. The authors wish to thank Dr. Mike Wells for thoughtful input on many drafts of the manuscript.

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, AL, 35115, USA

    Brett D. Noerager & Virginia A. Davis

  2. Department of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Xin Xu, Caleb W. Jones, J. Edwin Blalock & Patricia L. Jackson

  3. Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Caleb W. Jones, Svetlana Okafor & Alicia Whitehead

  4. UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    J. Edwin Blalock & Patricia L. Jackson

  5. UAB Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Patricia L. Jackson

  6. Birmingham VA Medical Center, Birmingham, AL, 35233, USA

    Patricia L. Jackson

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  1. Brett D. Noerager
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Correspondence to Brett D. Noerager.

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Noerager, B.D., Xu, X., Davis, V.A. et al. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation. Inflammation 38, 2279–2287 (2015). https://doi.org/10.1007/s10753-015-0213-2

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