PMID- 36829517 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230228 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 12 IP - 2 DP - 2023 Feb 3 TI - Ageing-Induced Decline in Primary Myeloid Cell Phagocytosis Is Unaffected by Optineurin Insufficiency. LID - 10.3390/biology12020240 [doi] LID - 240 AB - Optineurin is a ubiquitin-binding adaptor protein involved in multiple cellular processes, including innate inflammatory signalling. Mutations in optineurin were found in amyotrophic lateral sclerosis, an adult-onset fatal neurodegenerative disease that targets motor neurons. Neurodegeneration results in generation of neuronal debris, which is primarily cleared by myeloid cells. To assess the role of optineurin in phagocytosis, we performed a flow cytometry-based phagocytic assay of apoptotic neuronal debris and E. coli bioparticles in bone marrow-derived macrophages (BMDMs), and primary neonatal microglia from wild-type (WT) and optineurin-insufficient (Optn(470T)) mice. We found no difference in phagocytosis efficiency and the accompanying cytokine secretion in WT and Optn(470T) BMDMs and microglia. This was true at both steady state and upon proinflammatory polarization with lipopolysaccharide. When we analysed the effect of ageing as a major risk factor for neurodegeneration, we found a substantial decrease in the percentage of phagocytic cells and proinflammatory cytokine secretion in BMDMs from 2-year-old mice. However, this ageing-induced phagocytic decline was unaffected by optineurin insufficiency. All together, these results indicate that ageing is the factor that perturbs normal phagocytosis and proinflammatory cytokine secretion, but that optineurin is dispensable for these processes. FAU - Peradinovic, Josip AU - Peradinovic J AD - Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia. FAU - Mohovic, Nikolina AU - Mohovic N AUID- ORCID: 0000-0001-7744-904X AD - Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia. FAU - Bulic, Katarina AU - Bulic K AD - Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia. FAU - Markovinovic, Andrea AU - Markovinovic A AUID- ORCID: 0000-0003-1656-3150 AD - Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9RT, UK. FAU - Cimbro, Raffaello AU - Cimbro R AD - Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia. FAU - Munitic, Ivana AU - Munitic I AD - Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia. LA - eng GR - IP-2018-01-8563/Croatian Science Foundation/ GR - 18-211-1369/University of Rijeka/ PT - Journal Article DEP - 20230203 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC9953198 OTO - NOTNLM OT - ageing OT - inflammation OT - neurodegeneration OT - optineurin OT - phagocytosis COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/02/26 06:01 PMCR- 2023/02/03 CRDT- 2023/02/25 01:03 PHST- 2022/12/23 00:00 [received] PHST- 2023/01/31 00:00 [revised] PHST- 2023/01/31 00:00 [accepted] PHST- 2023/02/25 01:03 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/02/26 06:01 [medline] PHST- 2023/02/03 00:00 [pmc-release] AID - biology12020240 [pii] AID - biology-12-00240 [pii] AID - 10.3390/biology12020240 [doi] PST - epublish SO - Biology (Basel). 2023 Feb 3;12(2):240. doi: 10.3390/biology12020240.