VLA-4 integrin

Porter, J.R., Archibald, S.C., and Brown, J.A. 2003. Dehydrophenylalanine derivatives as VLA-4 integrin antagonists. Bioorg. Med. Chem. Lett. 

Hidalgo, A., Sanz-Rodriguez, F., Rodriguez-Fernandez, J. L., Albella, B., Blaya, C., Wright, N., Cabanas, C., Prosper, F., Gutierrez-Ramos, J. C., and Teixido, J. (2001). Chemokine stromal cell-derived factor-1 alpha modulates VLA-4 integrin-dependent adhesion to... 

Escribese MM, Conde E, Martin A et al. 2007. Therapeutic effect of all-trans-mimoic acid (at-RA) on an autoimmune nephritis experimental model Role of the VLA-4 integrin. BMC Nephrol. 8 3. 

The leukocyte integrin a 4(3 1 (also known as VLA-4 and CD49d/CD29) is a cell adhesion receptor, which is predominantly expressed on lymphocytes, monocytes and eosinophils. VLA-4 is generally selective for the CS1 domain within fibronectin, with an essential requirement for LDV sequence for binding. VLA-4 also binds to VCAM-1 as a counter receptor. 

A 3D model of the fibrinogen-derived (very late antigen-4, VLA-4) inhibitor 4-[N -(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val was derived from the X-ray structure of the related integrin-binding region of the vascular cell adhesion molecule-1 (VCAM-1). A 3D pharmacophore was generated with the program Catalyst, and a 3D search was performed in 8624 molecules from... 

Natalizumab (Tysabri ) is a recombinant humanized IgG4 mAb that binds to the a4-integrin subunit of a4(31 (VLA-4) and oA M (LPAM-1) integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the a4-mediated adhesion of leukocytes to their respective receptors.103 104 The receptor for a4pi, vascular cell adhesion molecule-1 (VCAM-1), is expressed on activated endothelial cells and is... 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

Dutta AS, Gormley JJ, Coath M, et al. Potent cyclic peptide inhibitors of VLA-4 (a4 pi Integrin)-mediated cell adhesion. Discovery of compounds like cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg) (ZD7349) compatible with depot formulation. 7 Pept Sci 2000 6 398-412. 

Elices, M. J., Osborn, L., Takada, Y., Crouse, C., Luhowskyj, S., Hemler, M. E., and Lobb, R. R. (1990). VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60,577-584. 

IgG2a, IgG2b, IgGl, IgG3, IgA, IgE Fibronectin Laminin Receptors Mannose, fucose, galactose Integrins (CFA-1, CR3, CR4, VLA-4)... 

The Pi integrins are also known as the very late antigen (VLA) subfamily because they were first identified on lymphocytes several days after activation.31 At present there are six members, all of which bind to proteins of the extracellular matrix (see Table 6.1). Unlike the other molecules, VLA-4 (CD49d) is found on the majority of unstimulated T lymphocytes, its expression being higher on memory than naive cells.32 It contributes to T-cell adhesion to inflamed endothelium by interacting with VCAM-1 and, as we shall see later, VLA-4 facilitates T-cell infiltration across the BBB in EAE. 

Shimizu, Y., van Seventer, G., Morgan, K. J., and Shaw, S., Role of adhesion molecules in T-cell recognition. Fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-6) in expression, binding and costimulation, Immunol. Rev., 114, 109, 1992. 

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