Endothelial cell interactions molecules

Table 47-14. Some molecules involved in leukocyte-endothelial cell interactions. ...

Although in the early 1990s several antibodies were developed that inhibited leukocyte-endothelial cell interaction to prevent e.g. allograft rejection or inflammatory processes [72], more effort is nowadays put into the development of small molecule antagonists and antisense oligonucleotides for this purpose [73,74], A selection of more recently reported clinical studies with antibodies is summarized in Table 1.2. 

The n-3 PUFAs are reported to reduce expression of endothelial adhesion molecules VCAM-1, E-selectin, and ICAM-1, therefore influencing leukocyte-endothelial cell interactions and leukocyte migration across the endothelium. 105,106 Oxidized EPA has been shown to be a more potent inhibitor of leukocyte-endothelial interaction, in vitro and in vivo, than EPA.107 Since EFAs regulate intercellular adhesion, it has been speculated that the skin changes that are observed in EFA deficiency, may be due, at least in part, to damaged cell adhesion.108 n-3 PUFAs and GLA supplementation enhance E-cadherin expression in cancer cells and this possibly reduces the invasiveness of these cells.109... 

As far as the inflammatory process concerns, the bulk of the data indicates that NO is pro-inflammatory. However, the conflicting notion that NO may be protective during an inflammatory insult also exists. For instance, leukocyte adhesion and infiltration, characteristic of the initial steps of inflammation, depends on the interaction of the leukocytes with the endothelial cell surface via glycoproteins (endothelial cell adhesion molecules, ECAM). NO modulates cytokine-induced ECAM expression in cultured endothelial cells in vitro by regulating the activation of NF-kB. Hence NO activity may result in this case as anti-inflammatory [50]. 

Risk and protective factors of atherosclerosis influence VCAM-1 expression [10,19]. A possible relation between VC AM expression and oxidized LDL was established when an important component of this modified lipoprotein, lysophosphatidylcholine, was shown to stimulate VCAM expression and increase adhesion of monocytes on endothelium in cell cultures [10,18,19]. Modified LDL and its constituents augment c)4 okine-activated VCAM-1 expression in human vascular endothelial cells [10,20]. In contrast, HDL inhibits cytokine-induced expression of endothelial cell adhesion molecules [10,21]. -3 Fatty acids have been found to decrease mRNA levels and surface expression of VCAM-1 in endothelial cells [10,22]. Aspirin inhibits induction of mRNA and cell surface expression of VCAM-1 by TNF-a and thereby inhibits monocyte adhesion on stimulated endothelial cells [10,23]. In contrast to ICAM-1, E-selectin, and P-selectin, endothelial VCAM-1 can mediate leukocyte adhesion via its sole interaction with the integrins 4P1 or 4P7 [10]. 

Lukacs NW, Stricter RM, Elner VM, Evanoff HL, Burdick M, Kunkel SL (1994) Intercellular adhesion molecule-1 mediates the expression of monocyte-derived MIP-1 alpha during monocyte-endothelial cell interactions. Blood 83 1174—1178... 

Lukacs, N. W., Stricter, R, M., Elner, V. M., Evanoff, H. L., Burdick, M. D., and Kunkel, S. L. (1994) Adhesion molecules mediate the expression of monocyte-derived MlP-1 alpha during monocyte-endothelial cell interactions. Blood S3,1174-1178. 

Quarmby S, Kumar P, Kumar S (1999) Radiation-induced normal tissue injury role of adhesion molecules in leukocyte-endothelial cell interactions. Int J Cancer 82 385-395... 

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... 

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. 

Yet another family of junction adhesion molecules (JAMs) was recently located at the tight junctions of both endothelial and epithelial cells. The intracellular domain of JAM-1 also interacts with structural and signaling proteins, such as ZO-1 and cingulin. Lastly, the molecular organization of the endothelial cell junctions includes two other cell-cell contact Ca2+-dependent cadherin-catenin systems. These make up the adherens junction common to all endothelial cell junctions. 

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