title: Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.
abstract: Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine; Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Rostyslav O
authors.initials: RO
authors.lastname: Bilyy
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine.
authors.forename: Tanya
authors.initials: T
authors.lastname: Shkandina
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine.
authors.forename: Andriy
authors.initials: A
authors.lastname: Tomin
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Muñoz
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franz
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Antonyuk
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine.
authors.forename: Yuriy Ya
authors.initials: YY
authors.lastname: Kit
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zirngibl
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Fürnrohr
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.affiliation: Department of Radiation Oncology, University of Munich, 81377 Munich, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.affiliation: Department of Medicine-V, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schiller
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005-Lviv, Ukraine.
authors.forename: Rostyslav S
authors.initials: RS
authors.lastname: Stoika
authors.affiliation: Department of Internal Medicine-3, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. Electronic address: martin.herrmann@UK-Erlangen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000494:pharmacology; D053181:Caspase 8 / Q000494:pharmacology; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D009439:Neuraminidase; D053148:Caspase 3; D053181:Caspase 8; D008358:Mannose; D005690:Galactose
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