| Entry |
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| Name |
Leukocyte transendothelial migration
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| 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.
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| Class |
09150 Organismal Systems; 09151 Immune system
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| Pathway map |
| map04670 | Leukocyte transendothelial migration |
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| Disease |
| H00099 | Leukocyte adhesion deficiency |
| H00742 | Neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome |
| H00840 | Band-like calcification with simplified gyration and polymicrogyria |
| H01255 | Juvenile-onset dystonia |
| H01387 | Activated PI3K-delta syndrome |
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| Other DBs |
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| Reference |
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| Authors |
van Buul JD, Hordijk PL. |
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| Title |
Signaling in leukocyte transendothelial migration. |
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| Journal |
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| Reference |
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| Authors |
Wittchen ES, van Buul JD, Burridge K, Worthylake RA. |
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| Title |
Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration. |
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| Journal |
Curr Opin Hematol 12:14-21 (2005) |
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| Reference |
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| Authors |
Barreiro O, Vicente-Manzanares M, Urzainqui A, Yanez-Mo M, Sanchez-Madrid F. |
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| Title |
Interactive protrusive structures during leukocyte adhesion and transendothelial migration. |
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| Journal |
Front Biosci 9:1849-63 (2004) |
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| Reference |
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| Authors |
Cook-Mills JM, Deem TL. |
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| Title |
Active participation of endothelial cells in inflammation. |
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| Journal |
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| Reference |
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| Authors |
Imhof BA, Aurrand-Lions M. |
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| Title |
Adhesion mechanisms regulating the migration of monocytes. |
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| Journal |
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| Reference |
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| Authors |
Deem TL, Cook-Mills JM. |
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| Title |
Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. |
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| Journal |
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| Reference |
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| Authors |
Etienne-Manneville S, Manneville JB, Adamson P, Wilbourn B, Greenwood J, Couraud PO. |
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| Title |
ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. |
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| Journal |
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| Reference |
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| Authors |
Chavakis T, Preissner KT, Santoso S. |
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| Title |
Leukocyte trans-endothelial migration: JAMs add new pieces to the puzzle. |
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| Journal |
Thromb Haemost 89:13-7 (2003) |
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| Reference |
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| Authors |
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. |
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| Title |
Tec family kinases in T lymphocyte development and function. |
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| Journal |
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| KO pathway |
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