Homing Receptors and Vascular Addressins

I N 1985, a review article appeared in this journal that examined the interactions of leukocytes with vascular endothelium during an immune or inflammatory response.’ The basic physiology of leukocyte emigration as well as disease states in which alterations of leukocyte-endothelial interactions may contribute to pathology were discussed. Since then there has been an explosion of interest in this topic. This explosion has been fueled by remarkable advances in the elucidation of the molecular basis of leukocyte adherence to endothelium and the potential for new therapies directed at these adhesion molecules.* Before 1985 only a single protein involved in leukocyte adherence to endothelium had clearly been identified immunologically-the murine lymphocyte homing receptor gpy””e’.3 In the subsequent years nine endothelial and nine leukocyte surface proteins involved in this heterotypic adhesion have been molecularly cloned (Fig 1, A and B). In addition, several other distinct leukocyte and endothelial molecules have been identified functionally or immunologically (Fig 1C). In this review, we focus on the expression, regulation, and function of the endothelial proteins known to be involved in the adhesion of leukocytes. We also consider the leukocyte counter-receptors for these proteins, and examine the current model of the sequential steps involved in leukocyte emigration to sites of inflammation. Finally, the use of “anti-adhesion” therapy in animal models of several diseases is reviewed. To provide a detailed review we have focused solely on the role of these adhesion proteins in leukocyte-endothelial interactions. We do not address the many additional functions subserved by these molecules such as binding of parasites (eg, malaria4,’), viruses (eg, rhinovirush.’), tumor cells,8 and hematopoietic precursors,Y”’ or their participation in signal transduction.’3”s Finally, although we have attempted to be comprehensive with respect to several aspects of leukocyte-endothelial adhesive interactions, we have undoubtedly overlooked some important contributions in these areas, and we apologize for these oversights. The interested reader may wish to consider other recent reviews on this topic,’”’’ particularly those relating to altered expression of adhesion molecules in human