Macrophages Discriminate Glycosylation Patterns of Apoptotic Cell-derived Microparticles

作者:Bilyy Rostyslav O; Shkandina Tanya; Tomin Andriy; Munoz Luis E; Franz Sandra; Antonyuk Volodymyr; Kit Yuriy Ya; Zirngibl Matthias; Fuernrohr Barbara G; Janko Christina; Lauber Kirsten; Schiller Martin; Schett Georg; Stoika Rostyslav S; Herrmann Martin*
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(1): 496-503.
DOI:10.1074/jbc.M111.273144

摘要

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.

  • 出版日期2012-1-2