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 mediated by several adhesive molecules expressed both on the leukocyte and endothelial membrane. In the early phases of inflammation, leukocytes transiently adhere to the vessel wall in a process termed "rolling". Rolling of leukocytes is mediated by a family of adhesive molecules called selectins, expressed both on the leukocyte and endothelial surface. Other adhesive molecules and chemotactic agents act in a complementary way, with selectins stabilizing polymorphonuclear cell adhesion and mediating their transendothelial migration into the inflamed foci. In particular, leukocyte beta 2 integrins present on the leukocyte membrane, binding to two adhesive immunoglobulins (ICAM-1 and ICAM-2) on the endothelial surface. Monocytes and lymphocytes also express the integrin VLA-4 (alpha 4 beta 1) which is the ligand of the immunoglobulin VCAM-1 on endothelial cells. It is still unknown how leukocytes can migrate through the inter-endothelial junctions. An interesting possibility is that leukocyte adhesion to endothelial cells could trigger intracellular signals that in turn can mediate junction disassembly. An understanding 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.