Identification of novel neutrophil very long chain plasmalogen molecular species and their myeloperoxidase mediated oxidation products in human sepsis
Kaushalya Amunugama,
Matthew J. Jellinek,
Megan P. Kilroy,
Carolyn J. Albert,
Valerio Rasi,
Daniel F. Hoft,
Michael G.S. Shashaty,
Nuala J. Meyer,
David A. Ford
Affiliations
Kaushalya Amunugama
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Matthew J. Jellinek
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Megan P. Kilroy
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Carolyn J. Albert
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Valerio Rasi
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Daniel F. Hoft
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA
Michael G.S. Shashaty
Pulmonary, Allergy, Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA; Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104-6021, USA
Nuala J. Meyer
Pulmonary, Allergy, Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA; Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104-6021, USA
David A. Ford
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA; Corresponding author. Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 Grand Blvd., DRC 325 St, Louis, MO, 63104, USA.
Plasmalogens are a class of phospholipids containing vinyl ether linked aliphatic groups at the sn-1 position. Plasmalogens are known to contain 16- and 18-carbon aliphatic groups at the sn-1 position. Here, we reveal that the human neutrophil plasmenylethanolamine pool uniquely includes molecular species with very long carbon chain (VLC) aliphatic groups, including 20-, 22- and 24-carbon vinyl ether linked aliphatic groups at the sn-1 position. We identified these novel VLC plasmalogen species by electrospray ionization mass spectrometry methods. VLC plasmalogens were only found in the neutrophil plasmenylethanolamine pool. During neutrophil activation, VLC plasmenylethanolamines undergo myeloperoxidase-dependent oxidation to produce VLC 2-chlorofatty aldehyde and its oxidation product, 2-chlorofatty acid (2-ClFA). Furthermore, plasma concentrations of VLC 2-ClFA are elevated in human sepsis. These studies demonstrate for the first time VLC plasmenylethanolamine molecular species, their myeloperoxidase-mediated chlorolipid products and the presence of these chlorolipids in human sepsis.