KEGG   PATHWAY: map04670Help
Entry
map04670                    Pathway                                

Name
Leukocyte transendothelial migration
Description
Leukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. A leukocyte adherent to CAMs on the endothelial cells moves forward by leading-edge protrusion and retraction of its tail. In this process, alphaL /beta2 integrin activates through Vav1, RhoA, which subsequently activates the kinase p160ROCK. ROCK activation leads to MLC phosphorylation, resulting in retraction of the actin cytoskeleton. Moreover, Leukocytes activate endothelial cell signals that stimulate endothelial cell retraction during localized dissociation of the endothelial cell junctions. ICAM-1-mediated signals activate an endothelial cell calcium flux and PKC, which are required for ICAM-1 dependent leukocyte migration. VCAM-1 is involved in the opening of the "endothelial passage" through which leukocytes can extravasate. In this regard, VCAM-1 ligation induces NADPH oxidase activation and the production of reactive oxygen species (ROS) in a Rac-mediated manner, with subsequent activation of matrix metallopoteinases and loss of VE-cadherin-mediated adhesion.
Class
09150 Organismal Systems; 09151 Immune system
BRITE hierarchy
Pathway map
map04670  Leukocyte transendothelial migration
map04670

Ortholog table
Disease
H00099  Leukocyte adhesion deficiency
H00742  Neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome
H00840  Band-like calcification with simplified gyration and polymicrogyria
H00947  Pilomatricoma
H01018  Metachondromatosis
H01255  Juvenile-onset dystonia
H01387  Activated PI3K-delta syndrome
Other DBs
GO: 0050900
Reference
  Authors
van Buul JD, Hordijk PL.
  Title
Signaling in leukocyte transendothelial migration.
  Journal
Arterioscler Thromb Vasc Biol 24:824-33 (2004)
DOI:10.1161/01.ATV.0000122854.76267.5c
Reference
  Authors
Wittchen ES, van Buul JD, Burridge K, Worthylake RA.
  Title
Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration.
  Journal
Curr Opin Hematol 12:14-21 (2005)
Reference
  Authors
Barreiro O, Vicente-Manzanares M, Urzainqui A, Yanez-Mo M, Sanchez-Madrid F.
  Title
Interactive protrusive structures during leukocyte adhesion and transendothelial migration.
  Journal
Front Biosci 9:1849-63 (2004)
Reference
  Authors
Cook-Mills JM, Deem TL.
  Title
Active participation of endothelial cells in inflammation.
  Journal
J Leukoc Biol 77:487-95 (2005)
DOI:10.1189/jlb.0904554
Reference
  Authors
Imhof BA, Aurrand-Lions M.
  Title
Adhesion mechanisms regulating the migration of monocytes.
  Journal
Nat Rev Immunol 4:432-44 (2004)
DOI:10.1038/nri1375
Reference
  Authors
Deem TL, Cook-Mills JM.
  Title
Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species.
  Journal
Blood 104:2385-93 (2004)
DOI:10.1182/blood-2004-02-0665
Reference
  Authors
Etienne-Manneville S, Manneville JB, Adamson P, Wilbourn B, Greenwood J, Couraud PO.
  Title
ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines.
  Journal
J Immunol 165:3375-83 (2000)
DOI:10.4049/jimmunol.165.6.3375
Reference
  Authors
Chavakis T, Preissner KT, Santoso S.
  Title
Leukocyte trans-endothelial migration: JAMs add new pieces to the puzzle.
  Journal
Thromb Haemost 89:13-7 (2003)
Reference
  Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
  Title
Tec family kinases in T lymphocyte development and function.
  Journal
Annu Rev Immunol 23:549-600 (2005)
DOI:10.1146/annurev.immunol.22.012703.104743
KO pathway
ko04670   

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