Senescence and quiescence induced compromised function in cultured macrophages

• Published in: Biomaterials Vol. 33; no. 30; pp. 7497 - 7507
• Main Authors: Holt, Dolly J, Grainger, David W
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2012
• Subjects: Advanced Basic Science; Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cell Cycle - drug effects; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Cellular Senescence - drug effects; Dentistry; Foreign body response; In vitro culture; Ki-67 Antigen - metabolism; Lipopolysaccharides - pharmacology; Macrophage; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Microspheres; Phagocytosis; Phagocytosis - drug effects; Phenotype; Quiescence; Senescence; Foreign body response; Senescence; Phagocytosis; In vitro culture; Macrophage; Quiescence
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.06.099

Abstract Implants are predisposed to infection even years after implantation, despite ostensibly being surrounded by innumerable macrophages as part of the host foreign body response. The local implant environment could adversely influence the implant-associated macrophage phenotype, proliferative capacity, activation states, and ability to neutralize pathogens. This study monitored cultured macrophage proliferative states and phagocytotic competence on tissue culture plastic to address the hypothesis that extended contact with foreign materials alters macrophage phenotype. That such macrophage alterations might also occur around implants has significance to the foreign body response, infection, cancer, autoimmune and other diseases. Specifically, multiple indicators of macrophage proliferation in various culture conditions, including cell confluence, long-term culture (21 days), lipopolysaccharide (LPS) stimulation, passaging, and mitogenic stimulation are reported. Importantly, primary murine macrophages became quiescent at high confluence and senescent during long-term culture. Senescent macrophages significantly reduced their ability to phagocytose particles, while quiescent macrophages did not. Cell senescence and quiescence were not observed with repeated passaging. Primary macrophage stimulation with LPS delayed senescence but did not eliminate it. These results prompt the conclusion that both cell quiescence and senescence are observed under common macrophage culture conditions and could alter macrophage behavior and phenotypes in extended in vitro culture, such as the ability to phagocytose. Such macrophage transitions around foreign bodies in vivo are not documented: quiescence and senescence reported here in macrophage culture could be relevant to macrophage behavior both in vitro in bioassays and in vivo in the foreign body response and implant-centered infection.