Abstract
Clearance of apoptotic neutrophils by macrophages is important for both the successful resolution of acute inflammation and homeostasis. However, the dynamic process of phagocytosis of apoptotic neutrophils by macrophages and the fate of macrophages after the ingestion of apoptotic neutrophils has not been well documented. In the present study, we staged the recognition and tethering, internalization, digestion and exocytosis steps of phagocytosis of apoptotic neutrophils. Furthermore, we found that after the ingestion of apoptotic cells, a subset of macrophages underwent cell death by autophagy, apoptosis or oncosis as revealed by transmission electron microscopy and confocal microscopy combined with specific dyes. The percentage of autophagic, apoptotic and oncotic macrophages were 8.00%±2.00%, 12.33%±2.08%, and 3.66%±1.50%, respectively. These results indicated that after ingestion of apoptotic neutrophils, a subset of macrophages undergoes autophagy and apoptosis. We propose that autophagy of macrophages after the ingestion of apoptotic cells may be a new mechanism present in the resolution of inflammation.
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Kobayashi SD, Voyich JM, Burlak C, DeLeo FR. Neutrophils in the innate immune response. Arch Immunol Ther Exp (Warsz), 2005, 53: 505–517
Sladek Z, Rysanek D, Ryznarova H, Faldyna M. Neutrophil apoptosis during experimentally induced staphylococcus aureus mastitis. Vet Res, 2005, 36: 629–643
Watson RW, Redmond HP, Wang JH, Bouchier-Hayes D. Bacterial ingestion, tumor necrosis factor-alpha, and heat induce programmed cell death in activated neutrophils. Shock, 1996, 5: 47–51
Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol, 2003, 4: 897–901
Djaldetti M, Salman H, Bergman M, Djaldetti R, Bessler H. Phagocytosis—the mighty weapon of the silent warriors. Microsc Res Tech, 2002, 57: 421–431
Schagat TL, Wofford JA, Wright JR. Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J Immunol, 2001, 166: 2727–2733
Fadeel B, Orrenius S, Zhivotovsky B. Apoptosis in human disease: a new skin for the old ceremony? Biochem Biophys Res Commun, 1999, 266: 699–717
Choi JJ, Reich CF, Pisetsky DS. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunology, 2005, 115: 55–62
Odaka C, Mizuochi T, Yang J, Ding A. Murine macrophages produce secretory leukocyte protease inhibitor during clearance of apoptotic cells: implications for resolution of the inflammatory response. J Immunol, 2003, 171: 1507–1514
Lichtenberger C, Zakeri S, Baier K, Willheim M, Holub M, Reinisch W. A novel high-purity isolation method for human peripheral blood neutrophils permitting polymerase chain reaction-based mRNA studies. J Immunol Methods, 1999, 227: 75–84
Tan BH, Meinken C, Bastian M, Bruns H, Legaspi A, Ochoa MT, Krutzik SR, Bloom BR, Ganz T, Modlin RL, Stenger S. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens. J Immunol, 2006, 177: 1864–1871
Wang C, Wang J, Guo HF, Liu RY. Involvement of Annexin I in the dexamethasone-mediated upregulation of A549 cells phagocytosis of apoptotic eosinophils. Immunol Lett, 2007, 111: 103–110
Maderna P, Yona S, Perretti M, Godson C. Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone- treated macrophages and annexin-derived peptide Ac(2-26). J Immunol, 2005, 174: 3727–3733
Hart SP, Alexander KM, Dransfield I. Immune complexes bind preferentially to Fc gamma RIIA (CD32) on apoptotic neutrophils, leading to augmented phagocytosis by macrophages and release of proinflammatory cytokines. J Immunol, 2004, 172: 1882–1887
Shi Q, King RW. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature, 2005, 437: 1038–1042
Mignot C, Delarasse C, Escaich S, Della Gaspera B, Noé E, Colucci-Guyon E, Babinet C, Pekny M, Vicart P, Boespflug-Tanguy O, Dautigny A, Rodriguez D, Pham-Dinh D. Dynamics of mutated GFAP aggregates revealed by real-time imaging of an astrocyte model of Alexander disease. Exp Cell Res, 2007, 313: 2766–2779
Zhu J-h, Horbinski C, Guo F, Watkins S, Uchiyama Y, Chu CT. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death. Am J Pathol, 2007, 170: 75–86
Guerin PJ, Furtak T, Eng K, Gauthier ER. Oxidative stress is not required for the induction of apoptosis upon glutamine starvation of Sp2/0-Ag14 hybridoma cells. Eur J Cell Biol, 2006, 85: 355–365
Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest, 1989, 83: 865–875
Ellis RE, Jacobson DM, Horvitz HR. Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics, 1991, 129: 79–94
Cvetanovic M, Mitchell JE, Patel V, Avner BS, Su Y, van der Saag PT, Witte PL, Fiore S, Levine JS, Ucker DS. Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity. J Biol Chem, 2006, 281: 20055–20067
Hoffmann PR, deCathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, Ridley AJ, Fadok VA, Henson PM. Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol, 2001, 155: 649–660
deCathelineau AM, Henson PM. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays Biochem, 2003, 39: 105–117
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of lrp on the phagocyte. Cell, 2005, 123: 321–334
Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol, 1995, 146: 3–15
Levin S. Apoptosis, necrosis, or oncosis: what is your diagnosis? A report from the cell death nomenclature committee of the society of toxicologic pathologists. Toxicol Sci, 1998, 41: 155–156
Frankenberg T, Kirschnek S, Hacker H, Häcker G. Phagocytosis- induced apoptosis of macrophages is linked to uptake, killing and degradation of bacteria. Eur J Immunol, 2008, 38: 204–215
Amer AO, Swanson MS. Autophagy is an immediate macrophage response to legionella pneumophila. Cell Microbiol, 2005, 7: 765–778
Zhou H, Kobzik L. Effect of concentrated ambient particles on macrophage phagocytosis and killing of streptococcus pneumoniae. Am J Respir Cell Mol Biol, 2007, 36: 460–465
Bhasin M, Wu M, Tsirka SE. Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis. BMC Immunol, 2007, 8: 10
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Wang, J., Huang, W., Wang, C. et al. Dynamic process of phagocytosis and forms of macrophage cell death induced by ingestion of apoptotic neutrophils. Sci. China Life Sci. 57, 1018–1023 (2014). https://doi.org/10.1007/s11427-014-4726-y
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DOI: https://doi.org/10.1007/s11427-014-4726-y