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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles
Rostyslav O Bilyy1, Tanya Shkandina2, Andriy Tomin2
1Institute 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.
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.
Insights
Apoptotic cells release distinct membranous particles (scMPs) from the endoplasmic reticulum or plasma membrane. These particles have unique surface markers that may explain autoimmune diseases like lupus.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Inappropriate clearance of apoptotic cells is linked to autoimmune diseases such as systemic lupus erythematosus.
- Apoptotic cells undergo significant structural and biochemical changes during programmed cell death.
Purpose of the Study:
- To investigate the distinct types of subcellular membranous particles (scMPs) released by apoptotic cells.
- To elucidate the immunological properties and origins of these scMPs and their role in disease.
Main Methods:
- Characterization of scMPs derived from the endoplasmic reticulum (ER) and plasma membrane.
- Analysis of glycotopes and sialidase activity on scMP surfaces.
- Investigation of caspase-dependent mechanisms regulating sialidase activity during apoptosis.
Main Results:
- Apoptotic cells release ER-derived and plasma membrane-derived scMPs.
- Both scMP types display desialylated glycotopes due to exposed immature glycoproteins or sialidase activity.
- Caspase 3 cleavage of sialidase Neu1 increases surface sialidase activity during apoptosis.
- ER-derived blebs with immature mannosidic glycoepitopes are preferentially cleared by macrophages.
- Plasma membrane-derived blebs contain DNA and histones but lack nuclear envelope components.
Conclusions:
- Two immunologically distinct types of apoptotic blebs exist, originating from the ER and plasma membrane.
- Desialylation of scMPs, mediated by caspase-activated sialidases, is a key feature.
- These findings offer new insights into the pathogenesis of clearance-related autoimmune diseases.
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