VCAMs

P-selectin, VEGFR2, VCAM, pPAR, CD55, Eotaxin-3, MCP-1... 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Members of the immunglobulin gene superfamily (VCAM-1, ICAM-1, ICAM-2)... 

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. 

The integrin a 4(3 7 is restricted to leukocytes and can bind not only to VCAM1 and fibronectin, but also to MAdCAM the mucosal addressin or homing receptor, which contains immunoglobulin-like domains related to VCAM-1. 

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... 

Sustained NF-kB activation, TNF-a, IL-1, proliferation, signals (M-CSF, G-CSF), chemotaxis (MCP-1), adhesion (VCAM-1, ICAM-1), thrombogenesis (TF)... 

The cell-to-cell interaction following the expression of adhesion molecules (ICAM-1, VCAM-1 and selectin) in endothelial cells induced by cytokines treatment has been reported to be blocked by hydroflavones and flavanols. Apigenin, the most potent flavone tested in this study, inhibited the expression... 

FRUEBis J, GONZALEZ v, siLVESTRE M and PALiNSKi w (1997) Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early sihsro genss.is, Arteriosclerosis, Thrombosis and Vascular Biology 17, 1289-302. 

NF-xB activates genes encoding MHC class I antigens, IL-1, TNFa, IL-6, the interleukin-2 (IL-2) receptor, some acute-phase proteins and the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) (lademarco... 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

VCAM, VCAM-1 Vascular ceU adhesion molecule, -1, also known as inducible cell adhesion molecule MW 110 kD (INCAM-110)... 

Papayannopoulou T, Craddock C, Nakamoto B, Priestley GV, Wolf NS. The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement... 

Liao Z, Roos JW, Hildreth JE. Increased infectivity of HIV type 1 particles bound to cell surface and solid-phase ICAM-1 and VCAM-1 through acquired adhesion molecules LFA-1 and VLA-4. AIDS Res Hum Retroviruses 2000 16(4) 355-366. 

Peterson JW, Bo L, Mork S, et al. VCAM-l-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions. J Neuropathol Exp Neurol 2002 61 539-546. 

C8. Carlos, T Swartz, R Kovach, N. L., Yee, E., Rosso, M., Osbom, L. C Rosso, G., Newman, B Lobb, R., and Harlan, J., Vascular cell adhesion molecule-1 (VCAM-1) mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 76, 965-970 (1990). 

Halichlorine 11 is a structurally unique alkaloid that was isolated from the sponge Halichondria okadai and found to act as an inhibitor of the induction of vascular cell adhesion molecule (VCAM-1), a potential target in the development of drugs for the treatment of several vascular diseases. The strategies employed for the construction of its spiroquinolizidine unit are summarized in Scheme 106. 

The study on the differential expression of various candidate targets by two different endothelial cells in culture revealed that the major effect of HU was restricted to ET-1 and ICAM-1 and to a limited extent to VCAM-1 in both cell types [26]. Hence only these factors will be discussed in detail. 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

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