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Complement dependent TNFα production in neutrophil-like HL60 cells
Neutrophils develop in the bone marrow (BM) from hematopoietic stem cells (HSCs) through a series of progenitor cells and mature neutrophils play a critical role in the human immune system. Previous studies revealed that tumor necrosis factor α (TNFα) produced by immature neutrophils contributes to...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130347/ https://www.ncbi.nlm.nih.gov/pubmed/37125077 http://dx.doi.org/10.1016/j.bbrep.2023.101465 |
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author | Tabata, Hiroyuki Morita, Hiroyuki Kouyama, Kenichi Tohyama, Yumi |
author_facet | Tabata, Hiroyuki Morita, Hiroyuki Kouyama, Kenichi Tohyama, Yumi |
author_sort | Tabata, Hiroyuki |
collection | PubMed |
description | Neutrophils develop in the bone marrow (BM) from hematopoietic stem cells (HSCs) through a series of progenitor cells and mature neutrophils play a critical role in the human immune system. Previous studies revealed that tumor necrosis factor α (TNFα) produced by immature neutrophils contributes to HSCs development and vascular regeneration in the BM niche. However, the precise mechanism of TNFα production in immature neutrophils remains unclear. This study aims to assess the relationship between complement C3 activation and TNFα production from immature neutrophils. We investigated the regulatory mechanism of TNFα production by complement components in neutrophil-like HL60 cells. Flow cytometric analysis showed that C3a receptor (C3aR) and C3bi receptor (CR3, Mac-1, CD11b/CD18, integrin αMβ2) are expressed on the surface of neutrophil-like HL60 cells. We found that zymosan-treated human serum leads to TNFα production in neutrophil-like HL60 cells, but not in human polymorphonuclear cells (PMNs). A C3-convertase inhibitor, compstatin suppresses TNFα production. These data suggest that the TNFα production is mediated by complement C3 activation. Furthermore, the TNFα production is enhanced by Ca(2+) elevating agents, thapsigargin (TG), but is suppressed by treatment with Ca(2+) chelators, EGTA, or BAPTA-AM. In addition, the soluble TNFα production is suppressed by treatment with immobilized-fibrinogen or -fibronectin. Thus, the TNFα production is enhanced by intracellular Ca(2+) elevation and is negatively regulated by the interaction between the neutrophil-like HL60 cells and fibrinogen or fibronectin. |
format | Online Article Text |
id | pubmed-10130347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101303472023-04-27 Complement dependent TNFα production in neutrophil-like HL60 cells Tabata, Hiroyuki Morita, Hiroyuki Kouyama, Kenichi Tohyama, Yumi Biochem Biophys Rep Research Article Neutrophils develop in the bone marrow (BM) from hematopoietic stem cells (HSCs) through a series of progenitor cells and mature neutrophils play a critical role in the human immune system. Previous studies revealed that tumor necrosis factor α (TNFα) produced by immature neutrophils contributes to HSCs development and vascular regeneration in the BM niche. However, the precise mechanism of TNFα production in immature neutrophils remains unclear. This study aims to assess the relationship between complement C3 activation and TNFα production from immature neutrophils. We investigated the regulatory mechanism of TNFα production by complement components in neutrophil-like HL60 cells. Flow cytometric analysis showed that C3a receptor (C3aR) and C3bi receptor (CR3, Mac-1, CD11b/CD18, integrin αMβ2) are expressed on the surface of neutrophil-like HL60 cells. We found that zymosan-treated human serum leads to TNFα production in neutrophil-like HL60 cells, but not in human polymorphonuclear cells (PMNs). A C3-convertase inhibitor, compstatin suppresses TNFα production. These data suggest that the TNFα production is mediated by complement C3 activation. Furthermore, the TNFα production is enhanced by Ca(2+) elevating agents, thapsigargin (TG), but is suppressed by treatment with Ca(2+) chelators, EGTA, or BAPTA-AM. In addition, the soluble TNFα production is suppressed by treatment with immobilized-fibrinogen or -fibronectin. Thus, the TNFα production is enhanced by intracellular Ca(2+) elevation and is negatively regulated by the interaction between the neutrophil-like HL60 cells and fibrinogen or fibronectin. Elsevier 2023-04-14 /pmc/articles/PMC10130347/ /pubmed/37125077 http://dx.doi.org/10.1016/j.bbrep.2023.101465 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Tabata, Hiroyuki Morita, Hiroyuki Kouyama, Kenichi Tohyama, Yumi Complement dependent TNFα production in neutrophil-like HL60 cells |
title | Complement dependent TNFα production in neutrophil-like HL60 cells |
title_full | Complement dependent TNFα production in neutrophil-like HL60 cells |
title_fullStr | Complement dependent TNFα production in neutrophil-like HL60 cells |
title_full_unstemmed | Complement dependent TNFα production in neutrophil-like HL60 cells |
title_short | Complement dependent TNFα production in neutrophil-like HL60 cells |
title_sort | complement dependent tnfα production in neutrophil-like hl60 cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130347/ https://www.ncbi.nlm.nih.gov/pubmed/37125077 http://dx.doi.org/10.1016/j.bbrep.2023.101465 |
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