LEUKOCYTE-ENDOTHELIAL CELL ADHESIVE RECEPTORS

The first step in leukocyte localization at inflammatory foci is their adhesion to the endothelial surface. This is a complex process mediat ed by several adhesive molecules expressed both on the leukocyte and e ndothelial membrane. In the early phases of inflammation, leukocytes t ransiently adhere to the vessel wall in a process termed ''rolling''. Rolling of leukocytes is mediated by a family of adhesive molecules ca lled selectins, expressed both on the leukocyte and endothelial surfac e. Other adhesive molecules and chemotactic agents act in a complement ary way, with selectins stabilizing polymorphonuclear cell adhesion an d mediating their transendothelial migration into the inflamed foci. I n particular, leukocyte beta2 integrins present on the leukocyte membr ane, binding to two adhesive immunoglobulins (ICAM-1 and ICAM-2) on th e endothelial surface. Monocytes and lymphocytes also express the inte grin VLA-4 (a4beta1) which is the ligand of the immunoglobulin VCAM-1 on endothelial cells. It is still unknown how leukocytes can migrate t hrough the interendothelial junctions. An interesting possibility is t hat leukocyte adhesion to endothelial cells could trigger intracellula r signals that in turn can mediate junction disassembly. An understand ing of the molecular mechanisms at the basis of leukocyte adhesion to the vessel wall and of their infiltration into the inflamed area could help to develop specific antagonists and a more targeted therapy for inflammatory diseases.