title: Suppression of macrophage-mediated phagocytosis of apoptotic cells by soluble β-glucan due to a failure of PKC-βII translocation.
abstract: If apoptotic cells are not removed efficiently, they may proceed to the stage of secondary necrosis, which would cause inflammation. Therefore, identification of cause(s) and agent(s) for down-modulating phagocytosis of apoptotic cells would help understand the pathologies. In this study we found that macrophage-mediated phagocytosis of apoptotic cells was suppressed by both soluble and particulate β-glucan. This suppression was not observed when secondary necrotic cells were used. The adhesion of apoptotic cells to macrophages was not suppressed by soluble β-glucan, suggesting that soluble β-glucan suppresses phagocytosis at a post-adhesion step. Experiments involving PKC inhibitors suggested that PKC-βII is required for phagocytosis of apoptotic cells but not secondary necrotic ones by macrophages. Translocation of GFP-PKC-βII from the cytoplasm to membranes occurred upon interaction with apoptotic cells but not secondary necrotic ones. Such translocation was inhibited by soluble β-glucan. Overall, this study suggests that suppression of macrophage-mediated phagocytosis of apoptotic cells by soluble β-glucan is due to a failure of PKC-βII translocation.
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Suzuno
authors.initials: S
authors.lastname: Sekiguchi
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Tomisawa
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ohki
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Div. of Molecular Medicine, Dept. of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan. Electronic address: yoshiro@biomol.sci.toho-u.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D010587:Phagocytosis / Q000187:drug effects*; D064546:Protein Kinase C beta / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects*; D047071:beta-Glucans / Q000494:pharmacology*
chemical_list: D047071:beta-Glucans; D064546:Protein Kinase C beta
keywords: Apoptotic cells; Macrophages; PKC-βII; Phagocytosis; Translocation; β-Glucan