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Adhesion molecules and inflammatory injury

1994; Wiley; Volume: 8; Issue: 8 Linguagem: Inglês

10.1096/fasebj.8.8.8181668

1530-6860

Steven Μ. Albelda, C. Wayne Smith, Peter A. Ward,

Blood Coagulation and Thrombosis Mechanisms

Neutrophil-endothelial cell interactions are mediated by interacting sets of cell adhesion molecules (CAMs) and chemoattractant/activator molecules to form an “adhesion cascade.” The initial phase of inflammation, a transient slowing of neutrophils in postcapillary venules, is mediated by selectins. Subsequently, firm adhesion of neutrophils to the vessel wall occurs via interaction of the CD11/GD18 (β2) integrins to endothelial ligands such as intercellular adhesion molecule-1 (ICAM-1). This binding requires activation of CD11/GD18 by exposure of the neutrophil to a variety of activating/chemoattractant molecules, such as platelet-activating factor or interleukin-8. Finally, transmigration into tissues occurs, a process that requires both a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecule-1 (PECAM-1). Several approaches have been used to probe the role of CAMs in vivo. These include the use of blocking antibodies, chimeric selectin-immunoglobulin proteins, sialyl Lewisx oligosaccharides and peptides, along with the study of humans and animals with genetically determined adhesion deficiencies. These studies demonstrate that CAM blockade can effectively inhibit inflammation; however, there appear to be clear differences in the adhesion requirements for particular types of inflammation. By understanding the CAM/chemoattractant profiles involved in specific disease states, it may be possible to precisely and effectively target therapy to a wide variety of inflammatory diseases.—Albelda, S. M., Smith, C. W., Ward, P. A. Adhesion molecules and inflammatory injury. FASEB J. 8: 504-512; 1994.