Integrins sites

Weitz-Schmidt, G., Welzenbach, K., Brinkmann, V., Kamata, T., Kallen, J., Bruns, C., Cottens, S., Takada, Y., and Hommel, U. (2001). Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med. 7, 687-692. 

Site directed delivery This approach of conjugating av 33 integrin ligand with a chemotherapeutic agent for optimal efficacy and safety in cancer is under investigation. Earlier work demonstrated the validity of this concept [10]. 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

The structure of the integrin family has been deduced largely from the cDNA sequences of the cloned genes. All integrins comprise a- and fl-subunits, and the ligand binding that occurs at the binding site comprises an interaction between the two subunits. The a-subunits can combine with dif-... 

The binding of integrins to certain ligands is mediated by a short amino acid sequence. Thus, the binding site for fibronectin is confined to a sequence of four amino acid residues, Arg-Gly-Asp-Ser (RGDS) (R7). Synthetic peptides containing the RGDS sequence prevented adhesion of cells to fibronectin (B4, R7) and also inhibited metastasis formation in animal models (B4, R7). 

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