Adhesion Molecules: Function and Inhibition by Klaus Ley

By Klaus Ley

Inflammatory phone recruitment calls for the concerted motion of a minimum of 5 significant units of adhesion molecules: integrins, immunoglobulin-like molecules, selectins, carbohydrate buildings serving as selectin ligands, and sure ectoenzymes. This quantity provides a accomplished review at the such a lot proper leukocyte and endothelial adhesion molecules. The chapters are written via leaders within the box and concentrate on the biology, constitution, functionality, and law of adhesion molecules. at present authorized adhesion molecule-based remedies are reviewed and an outlook for destiny techniques can be provided.

The e-book is of curiosity to clinicians and scientists from immunology, body structure, melanoma study, rheumatology, allergology, infectious illnesses, gastroenterology, pulmonology and cardiology.

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Inflammatory cellphone recruitment calls for the concerted motion of not less than 5 significant units of adhesion molecules: integrins, immunoglobulin-like molecules, selectins, carbohydrate buildings serving as selectin ligands, and likely ectoenzymes. This quantity supplies a accomplished evaluate at the so much suitable leukocyte and endothelial adhesion molecules.

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Both lymphocyte- and neutrophil-derived forms of sL-selectin have also been described in mouse [6] and rat [18] serum. Once cleaved, sL-selectin is stable with a t1/2 of ~20 h, a finding that helps explain the presence of relatively high concentrations (1–2 +g/ml) in human and mouse serum [5, 6, 19]. Importantly, sL-selectin retains functional activity as demonstrated by its ability to inhibit L-selectin-dependent leukocyte attachment to activated endothelium during in vitro [5] and in vivo [20] adhesion assays, and by inhibition of L-selectin-dependent in vivo lymphocyte migration [6].

J Exp Med 201: 1183–1189 Sperandio M, Smith ML, Forlow SB, Olson TS, Xia L, McEver RP, Ley K (2003) P-selectin glycoprotein ligand-1 mediates L-selectin-dependent leukocyte rolling in venules. J Exp Med 197: 1355–1363 Hirata T, Merrill-Skoloff G, Aab M, Yang J, Furie BC, Furie B (2000) P-selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration. , Schaub RG, McEver RP, Wagner DD (2003) Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A.

However, despite the identification of numerous ligands that can be recognized by L-selectin, defining any of these molecules as the physiological ligand for L-selectin remains difficult. For example, genetically targeted mice deficient in expression of GlyCAM-1, CD34 or both demonstrate normal L-selectin-dependent leukocyte adhesion and migration [53, 54]. Therefore, either these molecules do not function as physiological L-selectin ligands in vivo or there is a high degree of redundancy among ligands.

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