Anti-adhesion molecules

Cannella, B., Cross, A. H., and Raine, C. S., Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis, J. Neuroimmunol., 46, 43, 1993. 

In summary, the basic concept of the course of neural crest cell migration being controlled by adhesive interactions is now well established. However, the molecular events are likely to be complicated, featuring a balance between adhesive molecules (e.g. FN) and anti-adhesive molecules (e.g. CS-PG). Numerous other molecules in the microenvironment, which are recognized by numerous receptors on the cell surface, have not had precise functions assigned to them, but they could play a part in the fine control of migration in in vivo situations. 

Chiquet-Ehrismann, R. (1991) Anti-adhesive molecules of the extracellular matrix. Curr. Opin. Cell Biol. 3 800-804. 

While a lack of cell adhesion will not promote cell survival or proliferation, there are several physiological processes that depend upon cell detachment from the ECM. Examples of this necessary de-adhesion can be found in normal development and tissue homeostasis, as anti-adhesive molecules cause different levels of de-adhesion ranging from complete cell detachment to the localized detachment required for cell migration. Investigation of these anti-adhesive molecules is important, as their use in biomaterials may provide a means to generate matrices that are conducive to cell migration by mimicking the adhesive/anti-adhesive nature of the native ECM. 

Anti-adhesive molecules affect cell adhesion by changing the arrangement of cytoskeletal proteins and by altering signaling cascades. Specifically, tenascin-C, TSP-1, and SPARC all downregulate the actin stress fiber system and disrupt focal adhesions when added in solution to spread cells (Murphy-Ullrich, 2001 Orend and Chiquet-Ehrismann, 2000). Reorganization of the actin cytoskeleton is a major pathway by which... 

Anti-cytokine mAbs in rheumatoid arthritis 452 Anti-adhesion molecule mAbs 454 Anti-T cell mAbs in RA 455... 

Table appendix Adhesion Molecules Anti-integrins... 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

An anti-intracellular adhesion molecule-1 (anti-ICAM-1) antibody reduced neurological damage in a rabbit embolic model of stroke followed by thrombolysis with tissue-type plasminogen activator (tPA). When thrombolysis was delayed for 3 h following embolism, neither tPA nor the tPA/ICAM combination reduced neurological damage. 

The balance of opposing pro- and anti-platelet forces determines the overall hemostatic response. Successful hemostasis is achieved when assorted signal-transduction systems, mediators, white blood cells, and platelet receptors for agonists and adhesion molecules overcome the local resistance against platelet activation to generate... 

Exposure of the SECs to pathogens or cytokines produced by other cells during stress induces activation of the SECs and subsequent production of cytokines, eicosanoids, and/or adhesion molecules. For instance, after activation with EPS, a main component of the walls of gramnegative bacteria and a major inducer of inflammation and non-specific immune functions [20], SECs produce a number of pro- and anti-inflammatory cytokines. Pro-inflammatory cytokines shown to be produced were tumour necrosis factor alpha (TNFa) [26] interleukin-1 alpha/beta(IL-lo/p) [27] the major inducer of acute phase proteins interleukin-6 (IL-6) [28] and the neutrophil chemo-attractant interleukin-8 (IL-8) [29]. Anti-inflammatory cytokines shown to be produced were interleukin-10 (IL-10) [27] and hepatocyte growth factor (HGF) [30]. 

It should be noted, however, that mechanisms of action of most anti-angiogenic compounds are not well understood at present. For example, trombospondrn-1 (TSP-1) is able to inhibit tumour-associated angiogenesis, but when TSP-1 pellets were implanted into the ankles of AIA rats, it enhanced joint swelling and body weight loss in a dose- and time-dependent manner. These, possibly indirect, effects may be due to the involvement of TSP-1 in cell adhesion, as well as to its interactions with other adhesion molecules and inflammatory mediators [125]. 

Anti-adhesive effect. Green and roasted coffee, used in a treatment mixture and as a pretreatment on beads, inhibited the Strep tococcus mutans sucrose-independent adsorption to saliva-coated hydroxyapatite beads. The inhibition of Salmonelb mutans adsorption indicated that coffee-active molecules may adsorb to a host surface, preventing the tooth receptor from interacting with any bacterial adhesions. Among the known tested coffee components, trigonelline and nicotinic and chlorogenic acids are very... 

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