PMID- 19786543
OWN - NLM
STAT- MEDLINE
DCOM- 20091110
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 8
DP  - 2009 Oct 15
TI  - Role of endothelial TLR4 for neutrophil recruitment into central nervous system 
      microvessels in systemic inflammation.
PG  - 5244-50
LID - 10.4049/jimmunol.0901309 [doi]
AB  - 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.
FAU - Zhou, Hong
AU  - Zhou H
AD  - Immunology Research Group, Department Physiology and Biophysics, University of 
      Calgary, NW Calgary, Alberta, Canada.
FAU - Andonegui, Graciela
AU  - Andonegui G
FAU - Wong, Connie H Y
AU  - Wong CH
FAU - Kubes, Paul
AU  - Kubes P
LA  - eng
PT  - Journal Article
DEP - 20090928
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl1 protein, mouse)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (P-Selectin)
RN  - 0 (Receptors, Interleukin-8B)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Brain/immunology/metabolism
MH  - Cell Adhesion/drug effects/immunology
MH  - Cell Movement/drug effects/immunology
MH  - Central Nervous System/immunology
MH  - Chemokine CXCL1/immunology/metabolism
MH  - Chemokine CXCL2/immunology/metabolism
MH  - Encephalitis/*immunology
MH  - Endothelium, Vascular/*immunology
MH  - Interleukin-1beta/blood
MH  - Lipopolysaccharide Receptors/genetics/immunology/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microvessels/drug effects/immunology
MH  - *Neutrophil Infiltration
MH  - Neutrophils/drug effects/*immunology
MH  - P-Selectin/immunology/metabolism
MH  - Receptors, Interleukin-8B/genetics/immunology/metabolism
MH  - Toll-Like Receptor 4/genetics/*immunology
MH  - Tumor Necrosis Factor-alpha/blood
EDAT- 2009/09/30 06:00
MHDA- 2009/11/11 06:00
CRDT- 2009/09/30 06:00
PHST- 2009/09/30 06:00 [entrez]
PHST- 2009/09/30 06:00 [pubmed]
PHST- 2009/11/11 06:00 [medline]
AID - jimmunol.0901309 [pii]
AID - 10.4049/jimmunol.0901309 [doi]
PST - ppublish
SO  - J Immunol. 2009 Oct 15;183(8):5244-50. doi: 10.4049/jimmunol.0901309. Epub 2009 
      Sep 28.