ADHESION MOLECULES AND INFLAMMATORY INJURY

Neutrophil-endothelial cell interactions are mediated by interacting s ets of cell adhesion molecules (CAMs) and chemoattractant/activator mo lecules to form an ''adhesion cascade.'' The initial phase of inflamma tion, a transient slowing of neutrophils in postcapillary venules, is mediated by selectins. Subsequently, firm adhesion of neutrophils to t he vessel wall occurs via interaction of the CD11/CD18 (beta(2)) integ rins to endothelial ligands such as intercellular adhesion molecule-1 (ICAM-1). This binding requires activation of CD11/CD18 by exposure of the neutrophil to a variety of activating/chemoattractant molecules, such as platelet-activating factor or interleukin-8. Finally, transmig ration into tissues occurs, a process that requires both a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecul e-1 (PECAM-1). Several approaches have been used to probe the role of CAMs in vivo. These include the use of blocking antibodies, chimeric s electin-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 b lockade can effectively inhibit inflammation; however, there appear to be clear differences in the adhesion requirements for particular type s of inflammation. By understanding the CAM/chemoattractant profiles i nvolved in specific disease states, it may be possible to precisely an d effectively target therapy to a wide variety of inflammatory disease s.