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Impaired phagocytosis of apoptotic cells causes accumulation of bone marrow-derived macrophages in aged mice

  • Kim, Ok-Hee (Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University) ;
  • Kim, Hyojung (Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University) ;
  • Kang, Jinku (Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University) ;
  • Yang, Dongki (Department of Physiology, College of Medicine, Gachon University) ;
  • Kang, Yu-Hoi (Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd.) ;
  • Lee, Dae Ho (Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University) ;
  • Cheon, Gi Jeong (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Park, Sang Chul (Well Aging Research Center, DGIST) ;
  • Oh, Byung-Chul (Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University)
  • Received : 2016.09.29
  • Accepted : 2016.11.14
  • Published : 2017.01.31

Abstract

Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified age-dependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues.

Keywords

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