title: Cytoprotective effect of autophagy on phagocytosis of apoptotic cells by macrophages.
abstract: Clearance of the apoptotic cells by phagocytes plays pivotal roles in maintenance of tissue homeostasis, promotion of immunological tolerance and anti-inflammatory response. Recent studies show that autophagy is involved in phagocytosis of the apoptotic cells. However, contribution of autophagy to phagocytosis of the apoptotic cells by macrophages is not clearly defined. Here, we assessed cytoprotective effect of autophagy on clearance of the apoptotic cells. Apoptosis of murine splenic lymphocytes and human T-cell leukemia cells was induced with cyclophosphamide. After engulfment of the apoptotic cells, expression of Belin-1 and LC3 in macrophages was upregulated, the number of MDC-positive vesicles, LC3-positive autophagosomes and autophagic ultrastructures increased significantly. Autophagosome was fused with phagosome containing fragments of the nuclei or other debris of the apoptotic cells to form amphisome. Some cells in macrophages phagocytosing the apoptotic cells became apoptotic. After autophagy of macrophages was inhibited with 3-MA, viability and survival of macrophages reduced, phagocytosis of the apoptotic cells by macrophages deceased significantly. These results demonstrate that autophagy plays an important role in promoting clearance of the apoptotic cells by protecting macrophages from apoptosis during phagocytosis as well as degrading the contents of phagosomes via amphisome formation.
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Tan
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China. Electronic address: hjwang@shmu.edu.cn.
authors.forename: Hai-Jie
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D002103:Cadaverine / Q000031:analogs & derivatives / Q000378:metabolism; D002470:Cell Survival; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D019610:Cytoprotection; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology* / Q000648:ultrastructure; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D000071186:Beclin-1; D002103:Cadaverine; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C008542:monodansylcadaverine
keywords: Apoptosis; Apoptotic cells; Autophagy; Macrophages; Phagocytosis