Soluble CD93 is an apoptotic cell opsonin recognized by α x β 2 .

Autor: Blackburn JWD; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Lau DHC; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Liu EY; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Ellins J; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Vrieze AM; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Pawlak EN; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Dikeakos JD; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada., Heit B; Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2019 Apr; Vol. 49 (4), pp. 600-610. Date of Electronic Publication: 2019 Feb 07.
DOI: 10.1002/eji.201847801
Abstrakt: Efferocytosis is essential for homeostasis and prevention of the inflammatory and autoimmune diseases resulting from apoptotic cell lysis. CD93 is a transmembrane glycoprotein previously implicated in efferocytosis, with mutations in CD93 predisposing patients to efferocytosis-associated diseases. CD93 is a cell surface protein, which is proteolytically shed under inflammatory conditions, but it is unknown how CD93 mediates efferocytosis or whether its efferocytic activity is mediated by the soluble or membrane-bound form. Herein, using cell lines and human monocytes and macrophages, we demonstrate that soluble CD93 (sCD93) potently opsonizes apoptotic cells but not a broad range of microorganisms, whereas membrane-bound CD93 has no phagocytic, efferocytic, or tethering activity. Using mass spectrometry, we identified α x β 2 as the receptor that recognizes sCD93, and via deletion mutagenesis determined that sCD93 binds to apoptotic cells via its C-type lectin-like domain and to α x β 2 by its EGF-like repeats. The bridging of apoptotic cells to α x β 2 markedly enhanced efferocytosis by macrophages and was abrogated by α x β 2 knockdown. Combined, these data elucidate the mechanism by which CD93 regulates efferocytosis and identifies a previously unreported opsonin-receptor system utilized by phagocytes for the efferocytic clearance of apoptotic cells.
(© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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