title: Necroptotic cells release find-me signal and are engulfed without proinflammatory cytokine production.
abstract: Necroptosis is a form of caspase-independent programmed cell death which is mediated by the RIP1-RIP3 complex. Although phagocytosis of apoptotic cells has been extensively investigated, how necroptotic cells are engulfed has remained elusive. Here, we investigated how necroptotic cells attracted and were engulfed by macrophages. We found that necroptotic cells induced the migration of THP-1 cells in a transwell migration assay. Further analysis showed that ATP released from necroptotic cells acted as a find-me signal that induced the migration of THP-1 cells. We also found that Annexin V blocked phagocytosis of necroptotic cells by macrophages. Furthermore, necroptotic cells were shown to be silently cleared by macrophages without any proinflammatory cytokine production. These data uncover an evolutionarily conserved mechanism of the find-me signal in different types of cell death and immunological consequences between apoptotic and necroptotic cells during phagocytosis.
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China.|School of Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ju
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China. kpchen@ujs.edu.cn.
authors.forename: Keping
authors.initials: K
authors.lastname: Chen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017304:Annexin A5 / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000276:immunology*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: C119724:AGFG1 protein, human; D017304:Annexin A5; D016207:Cytokines; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D000255:Adenosine Triphosphate; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020169:Caspases
keywords: Find-me signal; Necroptosis; Phagocytosis