LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-α
Abstract
The deleterious effects of lipopolysaccharide (LPS) during endotoxic shock are associated with the secretion of tumor necrosis factor (TNF) and the production of nitric oxide (NO), both predominantly released by tissue macrophages. We analyzed the mechanism by which LPS induces apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF-alpha (early apoptotic events), and second, through the production of NO (late phase of apoptosis). (Blood. 2000;95:3823-3831)
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Cytokines are main promoters of apoptosis, particularly TNF.
“as cytokines are main promoters of apoptosis, particularly TNF [48, 49].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [49]
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- Authors
- Xaus, J., Comalada, M., Valledor, A. F., Lloberas, J., López-Soriano, F., Argilés, J. M., Bogdan, C., & Celada, A.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- From the Departament de Fisiologia (Biologia del Macròfag) and Fundació August Pi i Sunyer, Campus de Bellvitge; Departament de Bioquı́mica i Biologia Molecular, Facultat de Biologia Universitat de Barcelona, Barcelona, Spain; and the Institut für Klinische Mikrobiologie Immunologie und Hygiene, Universität Erlangen, Erlangen, Germany.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-06-15
- Volume
- 95
- Issue
- 12
- Pages
- 3823-3831
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1537320491
- Cited by
- 331
- References
- 4
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 15 · 2023: 19 · 2022: 14 · 2021: 14 · 2020: 14 · 2019: 14 · 2018: 23 · 2017: 11 · 2016: 15 · 2015: 17 · 2014: 14 · 2013: 13 · 2012: 14
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universitat de Barcelona
- Universidad de Cantabria
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- lipopolysaccharide, macrophage apoptosis, TNF-α, autocrine signaling, nitric oxide, inducible nitric oxide synthase, TNF receptor, p53, Bax, endotoxic shock, bone marrow-derived macrophages
- MeSH terms
- Animals, Bone Marrow Cells, Kinetics, Lipopolysaccharides, Macrophages, Mice, Inbred BALB C, Nitric Oxide, Penicillamine, Proto-Oncogene Proteins, Tumor Necrosis Factor-alpha, Antigens, CD, Genes, p53, Macrophage Colony-Stimulating Factor, Apoptosis, Receptors, Tumor Necrosis Factor, Mice, Knockout, Nitric Oxide Synthase, Proto-Oncogene Proteins c-bcl-2, Nitric Oxide Donors, S-Nitroso-N-Acetylpenicillamine, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, bcl-2-Associated X Protein, Mice, Nitric Oxide Synthase Type II, DNA Fragmentation
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