PMID- 30663448 OWN - NLM STAT- MEDLINE DCOM- 20200114 LR - 20200114 IS - 1532-4311 (Electronic) IS - 0882-0139 (Linking) VI - 48 IP - 7 DP - 2019 Oct TI - TNF May Negatively Regulate Phagocytosis of Devil Facial Tumour Disease Cells by Activated Macrophages. PG - 691-703 LID - 10.1080/08820139.2018.1515222 [doi] AB - Introduction: Macrophage phagocytosis of pathogens and tumour cells is an important early event in protection against infectious disease and cancer. As tumour necrosis factor alpha (TNF) is an important cytokine in macrophage activation, we investigated the involvement of TNF in macrophage phagocytosis of tumour cells. Methods: We used Devil Facial Tumour Disease (DFTD) cancer cells as the target tumour cells. The Tasmanian devil (Sarcophilus harrisii) population is threatened by the transmissible DFTD. Using DFTD cells provided the opportunity to determine if these cells can be phagocytosed and investigate requirement for TNF. As effector cells, bone marrow derived macrophages (BMDMs), generated from C57BL/6 wild type (B6.WT) and C57BL/6 TNF-/- (B6.TNF-/-) mice were used. Phagocytosis of DFTD cells was investigated by confocal microscopy and flow cytometry. Results: DFTD cells were consistently phagocytosed by B6.WT and B6.TNF-/- BMDMs with similar efficiency in vitro. Consequently the DFTD cells are not resistant to phagocytosis. Following activation by exposure to IFNgamma and LPS or LPS alone, B6.TNF-/- BMDMs had higher phagocytic efficiency and lower nitric oxide (NO) production compared to wild-type controls. In addition, NO seems to be unlikely to be the involved in phagocytosis efficiency in IFNgamma and LPS activated B6.TNF-/- macrophages and consequences thereof. Conclusion: Our results indicate that TNF is not required for IFNgamma and LPS or LPS alone activation of macrophage phagocytosis. TNF may negatively regulate macrophage phagocytosis of tumour cells. FAU - Li, Xinying AU - Li X AD - Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. AD - School of Life Science, Anhui Medical University , Hefei , People's Republic of China. FAU - Darby, Jocelyn AU - Darby J AD - Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. AD - School of Medicine, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. FAU - Lyons, A Bruce AU - Lyons AB AD - School of Medicine, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. FAU - Woods, Gregory M AU - Woods GM AD - Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. AD - School of Medicine, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. FAU - Korner, Heinrich AU - Korner H AUID- ORCID: 0000-0003-4610-2814 AD - Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania , Hobart , Tasmania , Australia. AD - Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Engineering Technology Research Centre of Anti-inflammatory and Immunodrugs in Anhui Province, Institute of Clinical Pharmacology, Anhui Medical University , Hefei, Anhui , People's Republic of China. LA - eng PT - Journal Article DEP - 20190119 PL - England TA - Immunol Invest JT - Immunological investigations JID - 8504629 RN - 0 (Lipopolysaccharides) RN - 0 (Tnf protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cells, Cultured MH - Facial Neoplasms/*immunology/pathology/*veterinary MH - Interferon-gamma/pharmacology MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/*immunology/metabolism MH - Marsupialia MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Nitric Oxide/metabolism MH - Phagocytosis MH - Tumor Necrosis Factor-alpha/deficiency/*immunology OTO - NOTNLM OT - Devil Facial Tumour disease OT - Macrophages OT - TNF OT - nitric oxide OT - phagocytosis EDAT- 2019/01/22 06:00 MHDA- 2020/01/15 06:00 CRDT- 2019/01/22 06:00 PHST- 2019/01/22 06:00 [pubmed] PHST- 2020/01/15 06:00 [medline] PHST- 2019/01/22 06:00 [entrez] AID - 10.1080/08820139.2018.1515222 [doi] PST - ppublish SO - Immunol Invest. 2019 Oct;48(7):691-703. doi: 10.1080/08820139.2018.1515222. Epub 2019 Jan 19.