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Cited by 223Neuroinflammation and Neurodegeneration MechanismsImmune Response and InflammationSepsis Diagnosis and Treatment

The Bacterial Endotoxin Lipopolysaccharide has the Ability to Target the Brain in Upregulating Its Membrane CD14 Receptor Within Specific Cellular Populations

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Lacroix, Steve, Feinstein, Doug, Rivest, Serge·1998·Brain Pathology
DOI 10.1111/j.1750-3639.1998.tb00189.xPMC PMC8098216
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Abstract

Systemic injection of the bacterial endotoxin lipopolysaccharide (LPS) provides a very good mean for increasing the release of proinflammatory cytokines by circulating monocytes and tissue macrophages. There is now considerable evidence that LPS exerts its action on mononuclear phagocytes via the cell surface receptor CD14. The aim of the present study was to verify the hypothesis that the brain has also the ability to express the gene encoding the LPS receptor, which may allow a direct action of the endotoxin onto specific cellular populations during blood sepsis. Adult male Sprague‐Dawley rats were sacrificed 1, 3, 6 and 24 h after systemic (i.v. or i.p.) injection of LPS or the vehicle solution. Brains were cut from the olfactory bulb to the medulla in 30‐μm coronal sections and mRNA encoding rat CD14 was assayed by in situ hybridization histochemistry using a specific 35 S‐labeled riboprobe. The results show low levels of CD14 mRNA in the leptomeninges, choroid plexus and along blood vessels of the brain microvasculature under basal conditions. Systemic injection of the bacterial endotoxin caused a profound increase in the expression of the gene encoding CD14 within these same structures as well as in the circumventricular organs (CVOs) the organum vasculosum of the lamina terminalis, subfornical organ, median eminence and area postrema. In most of these structures, the signal for CD14 mRNA was first detected at 1 h, reached a peak at 3 h post‐injection, declined at 6 h, and return to basal levels 24 h after LPS treatment. Quite interestingly, a migratory‐like pattern of CD14 positive cells was observed from all sensorial CVOs to deeper parenchymal brain 3 and 6 h after LPS injection. At 6 h post‐challenge, small positive cells were found throughout the entire parenchymal brain and dual‐labeling procedure indicated that different cells of myeloid origin have the ability to express CD14 in response to systemic LPS. These included CVO microglia, choroid plexus and leptomeninge macrophages, parenchymal and perivascular‐associated microglial cells, although specific nonmyeloid cells were also positive for the LPS receptor. These results provide the very first evidence of a direct role of LPS on specific cell populations of the central nervous system, which is likely to be responsible for the transcription of proinflammatory cytokines; first within accessible structures from the blood and thereafter through scattered parenchymal cells during severe sepsis.

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Crossref · 10.1111/j.1750-3639.1998.tb00189.x

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Research works printed but not linked: 2

  1. [4]4. Besedovsky H.O. and Del Rey A. ( 1996. ) Immune‐neuroendocrine interactions: Facts and hypotheses . Endocr. Rev. 17 : 64 – 102 . [DOI] [PubMed] [Google Scholar]
  2. [22]22. Lacroix S. and Rivest S. ( 1997. ) Functional circuitry in the brain of immune‐challenged rats: partial involvement of prostaglandins . J. Comp. Neurol. 387 : 307 – 324 . [DOI] [PubMed] [Google Scholar]

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Authors
Lacroix, S., Feinstein, D., & Rivest, S.
Affiliations
  • Centre hospitalier de l'Université Laval (CA)
  • Cornell University (US)
Corresponding author
Rivest, Serge
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
1998-10
Volume
8
Issue
4
Pages
625-640
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.1998.tb00189.x
PMC
PMC8098216
OpenAlex
W2135406130
Cited by
223
References
42
Citations by year
2025: 1 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 5 · 2014: 15 · 2013: 15 · 2012: 4
FWCI
6.00
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2743 d)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
lipopolysaccharide, CD14 receptor, brain, sepsis, circumventricular organs, choroid plexus, microglia, myeloid cells, neuroinflammation, organum vasculosum of the lamina terminalis, subfornical organ, area postrema
MeSH terms
Animals, Bacterial Toxins, Brain, Brain Chemistry, Cell Membrane, Enterotoxins, Immunohistochemistry, Injections, Intravenous, Lipopolysaccharides, Male, Receptors, Antigen, RNA Probes, Up-Regulation, Rats, Sprague-Dawley, In Situ Hybridization, Lipopolysaccharide Receptors, Escherichia coli Proteins, Rats

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