Adhesion molecules and inflammatory injury

Abstract

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 (β 2 ) 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 Lewis x 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.