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Cited by 174Neuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function StudiesImmune Response and Inflammation

Role of Endothelial TLR4 for Neutrophil Recruitment into Central Nervous System Microvessels in Systemic Inflammation

Zhou, Hong, Andonegui, Graciela, Wong, Connie H Y, Kubes, Paul·2009·The Journal of Immunology
DOI 10.4049/jimmunol.0901309
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Abstract

Brain inflammation is a frequent consequence of sepsis and septic shock. We imaged leukocyte recruitment in brain postcapillary venules induced by i.p. administration of LPS as a simple model of systemic inflammation. The i.p. injection of LPS (0.5 mg/kg) induced significant leukocyte rolling and adhesion in brain postcapillary venules of wild-type (WT) mice and more than 90% were neutrophils. However, no emigrated neutrophils were detected in brain parenchyma. High levels of TNF-α and IL-1β were detected in the plasma after LPS injection but a different profile (IL-1β but not TNF-α) was detected in the brain. LPS caused no recruitment in TLR4 knockout mice. In chimeric mice with TLR4-expressing resident cells but TLR4-deficient bone marrow-derived circulating cells, neutrophil rolling and adhesion was similar to WT mice. This observation is consistent with a requirement for resident cells in the LPS-induced neutrophil recruitment into brain microvessels. Transgenic mice engineered to express TLR4 exclusively on endothelial cells had a similar level of leukocyte recruitment in brain as WT mice in response to LPS. High dose LPS (10 mg/kg) led to neutrophil infiltration in the brain parenchyma in WT mice. High KC and MIP-2 production was observed from brain parenchyma microglial cells, and CXCR2 knockout mice failed to recruit neutrophils. However, neither neutrophil infiltration nor KC or MIP-2 was observed in endothelial TLR4 transgenic mice in response to this LPS dose. Our results demonstrate that direct endothelial activation is sufficient to mediate leukocyte rolling and adhesion in cerebral microvessels but not sufficient for emigration to brain parenchyma.

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  • BM-derived monocytes traffic to and influence inflammatory signaling in the brain in models of severe trauma or advanced disease states.

    “However, it has now been well demonstrated in models of severe trauma or advanced disease states that BM-derived monocytes traffic to and influence inflammatory signaling in the brain (Zhou et al, 2009;Grozdanov et al, 2014).”

    From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Zhou et al, 2009

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Authors
Zhou, H., Andonegui, G., Wong, C. H. Y., & Kubes, P.
Affiliations
University of Calgary (CA)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2009-10
Volume
183
Issue
8
Pages
5244-5250
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.0901309
OpenAlex
W2128021781
Cited by
174
References
27
Citations by year
2026: 4 · 2025: 6 · 2024: 11 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 12 · 2019: 7 · 2018: 12 · 2017: 12 · 2016: 14 · 2015: 14 · 2014: 3 · 2013: 17 · 2012: 12
FWCI
6.39
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
neutrophil recruitment, cerebral microvasculature, systemic inflammation, sepsis, septic shock, leukocyte rolling and adhesion, postcapillary venules, LPS, TNF-α, IL-1β, CXCR2, microglia, chimeric mice, TLR4 knockout mice
MeSH terms
Animals, Brain, Cell Adhesion, Cell Movement, Central Nervous System, Encephalitis, Endothelium, Vascular, Lipopolysaccharides, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Tumor Necrosis Factor-alpha, Mice, Knockout, Lipopolysaccharide Receptors, P-Selectin, Neutrophil Infiltration, Receptors, Interleukin-8B, Toll-Like Receptor 4, Mice, Interleukin-1beta, Chemokine CXCL1, Chemokine CXCL2, Microvessels

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