PMID- 18697212
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20130520
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 48
IP  - 4
DP  - 2008 Oct
TI  - Enhanced T cell transmigration across the murine liver sinusoidal endothelium is 
      mediated by transcytosis and surface presentation of chemokines.
PG  - 1262-72
LID - 10.1002/hep.22443 [doi]
AB  - Transmigration through the liver endothelium is a prerequisite for the 
      homeostatic balance of intrahepatic T cells and a key regulator of inflammatory 
      processes within the liver. Extravasation into the liver parenchyma is regulated 
      by the distinct expression patterns of adhesion molecules and chemokines and 
      their receptors on the lymphocyte and endothelial cell surface. In the present 
      study, we investigated whether liver sinusoidal endothelial cells (LSEC) inhibit 
      or support the chemokine-driven transmigration and differentially influence the 
      transmigration of pro-inflammatory or anti-inflammatory CD4(+) T cells, 
      indicating a mechanism of hepatic immunoregulation. Finally, the results shed 
      light on the molecular mechanisms by which LSEC modulate chemokine-dependent 
      transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif 
      chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and 
      memory CD4(+) T cells of a T helper 1, T helper 2, or interleukin-10-producing 
      phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo 
      isolated lung endothelia inhibited chemokine-driven transmigration. As for the 
      molecular mechanisms, chemokine-induced activation of LSEC was excluded by 
      blockage of G(i)-protein-coupled signaling and the use of knockout mice. After 
      preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced 
      transmigration as efficiently as in the presence of the soluble chemokine. 
      Blockage of transcytosis in LSEC significantly inhibited this effect, and this 
      suggested that chemokines taken up from the basolateral side and presented on the 
      luminal side of endothelial cells trigger T cell transmigration. CONCLUSION: Our 
      findings demonstrate a unique capacity of LSEC to present chemokines to 
      circulating lymphocytes and highlight the importance of endothelial cells for the 
      in vivo effects of chemokines. Chemokine presentation by LSEC could provide a 
      future therapeutic target for inhibiting lymphocyte immigration and suppressing 
      hepatic inflammation.
FAU - Schrage, Arnhild
AU  - Schrage A
AD  - Medizinische Klinik I, Campus Charite Benjamin Franklin, Berlin, Germany.
FAU - Wechsung, Katja
AU  - Wechsung K
FAU - Neumann, Katrin
AU  - Neumann K
FAU - Schumann, Michael
AU  - Schumann M
FAU - Schulzke, Jorg-Dieter
AU  - Schulzke JD
FAU - Engelhardt, Britta
AU  - Engelhardt B
FAU - Zeitz, Martin
AU  - Zeitz M
FAU - Hamann, Alf
AU  - Hamann A
FAU - Klugewitz, Katja
AU  - Klugewitz K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokine CXCL9)
RN  - 0 (Cxcr3 protein, mouse)
RN  - 0 (Receptors, CXCR3)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*cytology/drug effects/physiology
MH  - Cell Line
MH  - Cell Movement/drug effects/*physiology
MH  - Cells, Cultured
MH  - Chemokine CXCL12/*metabolism/pharmacology
MH  - Chemokine CXCL9/*metabolism/pharmacology
MH  - Endothelium/cytology/metabolism
MH  - Female
MH  - Liver/cytology/*metabolism
MH  - Lung/cytology/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Receptors, CXCR3/genetics/metabolism
MH  - Spleen/cytology/drug effects
MH  - Th1 Cells/cytology/drug effects
MH  - Th2 Cells/cytology/drug effects
EDAT- 2008/08/13 09:00
MHDA- 2008/10/28 09:00
CRDT- 2008/08/13 09:00
PHST- 2008/08/13 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/08/13 09:00 [entrez]
AID - 10.1002/hep.22443 [doi]
PST - ppublish
SO  - Hepatology. 2008 Oct;48(4):1262-72. doi: 10.1002/hep.22443.