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Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation.
J Immunol. 2009 Oct 15; 183(8):5244-50.JI

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-alpha and IL-1beta were detected in the plasma after LPS injection but a different profile (IL-1beta but not TNF-alpha) 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.

Authors+Show Affiliations

Immunology Research Group, Department Physiology and Biophysics, University of Calgary, NW Calgary, Alberta, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19786543

Citation

Zhou, Hong, et al. "Role of Endothelial TLR4 for Neutrophil Recruitment Into Central Nervous System Microvessels in Systemic Inflammation." Journal of Immunology (Baltimore, Md. : 1950), vol. 183, no. 8, 2009, pp. 5244-50.
Zhou H, Andonegui G, Wong CH, et al. Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation. J Immunol. 2009;183(8):5244-50.
Zhou, H., Andonegui, G., Wong, C. H., & Kubes, P. (2009). Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation. Journal of Immunology (Baltimore, Md. : 1950), 183(8), 5244-50. https://doi.org/10.4049/jimmunol.0901309
Zhou H, et al. Role of Endothelial TLR4 for Neutrophil Recruitment Into Central Nervous System Microvessels in Systemic Inflammation. J Immunol. 2009 Oct 15;183(8):5244-50. PubMed PMID: 19786543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation. AU - Zhou,Hong, AU - Andonegui,Graciela, AU - Wong,Connie H Y, AU - Kubes,Paul, Y1 - 2009/09/28/ PY - 2009/9/30/entrez PY - 2009/9/30/pubmed PY - 2009/11/11/medline SP - 5244 EP - 50 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 183 IS - 8 N2 - 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-alpha and IL-1beta were detected in the plasma after LPS injection but a different profile (IL-1beta but not TNF-alpha) 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/19786543/Role_of_endothelial_TLR4_for_neutrophil_recruitment_into_central_nervous_system_microvessels_in_systemic_inflammation_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=19786543 DB - PRIME DP - Unbound Medicine ER -