Adhesion molecules and inflammatory injury.
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/CD18 (beta 2) integrins 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, 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
SM
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104.
Smith
C W
CW
Ward
P A
PA
D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007249:Inflammation; D016023:Integrins; D007962:Leukocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D016028:Receptors, Leukocyte-Adhesion; D014699:Venules / Q000166:cytology* / Q000502:physiology
D015815:Cell Adhesion Molecules; D016023:Integrins; D016028:Receptors, Leukocyte-Adhesion