Cited by 291Immune Response and InflammationNF-κB Signaling PathwaysSepsis Diagnosis and Treatment

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A Novel Receptor Tyrosine Kinase, Mer, Inhibits TNF-α Production and Lipopolysaccharide-Induced Endotoxic Shock

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Camenisch, Todd D, Koller, Beverly H, Earp, H Shelton, Matsushima, Glenn K·1999·The Journal of Immunology

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Abstract

Abstract The regulation of monocyte function and the inhibition of TNF-α production during bacterial sepsis are critical in attenuating adverse host responses to endotoxemia. To study the function of a novel receptor tyrosine kinase, mer, that is expressed in monocytes, we generated mice (merkd) that lack the signaling tyrosine kinase domain. Upon LPS challenge, merkd animals died of endotoxic shock (15/17, 88.2%), whereas control wild-type mice survived (1/15, 6.7% died). Susceptible merkd mice exhibited edema, leukocyte infiltration, and signs of endotoxic shock that correlated with higher levels of TNF-α found in the serum of merkd mice as compared with wild-type control animals. Death due to LPS-induced endotoxic shock in merkd mice was blocked by administration of anti-TNF-α Ab, suggesting that overproduction of this cytokine was principally responsible for the heightened suseptibility. The increase in TNF-α production appeared to be the result of a substantial increase in the LPS-dependent activation of NF-κB nuclear translocation resulting in greater TNF-α production by macrophages from merkd mice. Thus, Mer receptor tyrosine kinase signaling participates in a novel inhibitory pathway in macrophages important for regulating TNF-α secretion and attenuating endotoxic shock.

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Authors: Camenisch, T. D., Koller, B. H., Earp, H. S., & Matsushima, G. K.
Affiliations: University of North Carolina at Chapel Hill (US)
ORCID: Camenisch, Todd D
Koller, Beverly H
Earp, H Shelton
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1999-03
Volume: 162
Issue: 6
Pages: 3498-3503
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.162.6.3498
OpenAlex: W4313344687
Cited by: 290
References: 31
Citations by year: 2026: 7 · 2025: 6 · 2024: 21 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 18 · 2019: 17 · 2018: 16 · 2017: 17 · 2016: 13 · 2015: 13 · 2014: 12 · 2013: 13 · 2012: 5
FWCI: 1.72
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
Funders: University of North Carolina at Chapel Hill
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Keywords: Mer receptor tyrosine kinase, TNF-alpha production, endotoxic shock, lipopolysaccharide, endotoxemia, sepsis, monocytes, macrophages, NF-κB nuclear translocation, anti-TNF-alpha antibody, receptor signaling

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A Novel Receptor Tyrosine Kinase, Mer, Inhibits TNF-α Production and Lipopolysaccharide-Induced Endotoxic Shock

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