PMID- 17182592
OWN - NLM
STAT- MEDLINE
DCOM- 20070306
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 1
DP  - 2007 Jan 1
TI  - Dendritic cell transmigration through brain microvessel endothelium is regulated 
      by MIP-1alpha chemokine and matrix metalloproteinases.
PG  - 520-9
AB  - Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the 
      exact mechanism regulating their traffic into the CNS remains to be defined. We 
      now report that MIP-1alpha increases the transmigration of bone marrow-derived, 
      GFP-labeled DCs across brain microvessel endothelial cell monolayers. 
      Furthermore, occludin, an important element of endothelial tight junctions, is 
      reorganized when DCs migrate across brain capillary endothelial cell monolayers 
      without causing significant changes in the barrier integrity as measured by 
      transendothelial electrical resistance. We show that DCs produce matrix 
      metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both 
      baseline and MIP-1alpha-induced DC transmigration. These observations suggest 
      that DC transmigration across brain endothelial cell monolayers is partly MMP 
      dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 
      costimulatory molecules and induce T cell proliferation, indicating that the 
      transmigration of DCs across brain endothelial cell monolayers contributes to the 
      maintenance of DC Ag-presenting function. The MMP dependence of DC migration 
      across brain endothelial cell monolayers raises the possibility that MMP blockers 
      may decrease the initiation of T cell recruitment and neuroinflammation in the 
      CNS.
FAU - Zozulya, Alla L
AU  - Zozulya AL
AD  - Department of Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA.
FAU - Reinke, Emily
AU  - Reinke E
FAU - Baiu, Dana C
AU  - Baiu DC
FAU - Karman, Jozsef
AU  - Karman J
FAU - Sandor, Matyas
AU  - Sandor M
FAU - Fabry, Zsuzsanna
AU  - Fabry Z
LA  - eng
GR  - R01-NS 37570-01A2/NS/NINDS NIH HHS/United States
GR  - R01 NS037570-07/NS/NINDS NIH HHS/United States
GR  - R01 NS037570-06/NS/NINDS NIH HHS/United States
GR  - R01 NS037570-05A1/NS/NINDS NIH HHS/United States
GR  - R01 NS037570/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, mouse)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Brain/*blood supply
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Movement/immunology
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Chemokines/pharmacology/physiology
MH  - Dendritic Cells/drug effects/enzymology/*immunology
MH  - Endothelium, Vascular/*immunology/ultrastructure
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Green Fluorescent Proteins/analysis/genetics
MH  - Lymphocyte Activation
MH  - Macrophage Inflammatory Proteins/pharmacology/*physiology
MH  - Matrix Metalloproteinase 2/physiology
MH  - Matrix Metalloproteinase 9/physiology
MH  - Matrix Metalloproteinase Inhibitors
MH  - Matrix Metalloproteinases/*physiology
MH  - Membrane Proteins/analysis/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Occludin
MH  - Tight Junctions/chemistry/ultrastructure
PMC - PMC1950722
MID - NIHMS25561
EDAT- 2006/12/22 09:00
MHDA- 2007/03/07 09:00
PMCR- 2008/01/01
CRDT- 2006/12/22 09:00
PHST- 2006/12/22 09:00 [pubmed]
PHST- 2007/03/07 09:00 [medline]
PHST- 2006/12/22 09:00 [entrez]
PHST- 2008/01/01 00:00 [pmc-release]
AID - 178/1/520 [pii]
AID - 10.4049/jimmunol.178.1.520 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jan 1;178(1):520-9. doi: 10.4049/jimmunol.178.1.520.