As with the complement components, a significant barrier to understanding the functions of cell-adhesion molecules is their nomenclature. Most adhesion molecules, especially those on leukocytes, which are relatively easy to analyze functionally, were originally named after the effects of specific monoclonal antibodies directed against them. Their names therefore bear no relation to their structural class. For instance, the leukocyte functional antigens LFA-1, LFA-2, and LFA-3 are actually members of two different protein families. In Fig. 3.29, the adhesion molecules relevant to innate immunity are grouped according to their molecular structure, which is shown in schematic form alongside their different names, sites of expression, and ligands. Three structural families of adhesion molecules are important for leukocyte recruitment. The selectins are membrane glycoproteins with a distal lectin-like domain that binds specific carbohydrate groups. Members of this family are induced on activated endothelium and initiate endothelium–leukocyte interactions by binding to fucosylated oligosaccharide ligands on passing leukocytes (see Fig. 3.29).
The next step in leukocyte recruitment depends on tighter adhesion, which is due to the binding of intercellular adhesion molecules (ICAMs) on the endothelium to heterodimeric proteins of the integrin family on leukocytes. ICAMs are single-pass membrane proteins that belong to the large superfamily of immunoglobulin-like proteins, which contain protein domains similar to those of immunoglobulins. The extracellular regions of ICAMs are composed of several immunoglobulin-like domains. An integrin molecule is composed
Fig. 3.29 Adhesion molecules involved in leukocyte interactions. Several structural families of adhesion molecules have a role in leukocyte migration, homing, and cell–cell interactions: the selectins, the integrins, and proteins of the immunoglobulin superfamily. The figure shows schematic representations of an example from each family, a list of other family members that participate in leukocyte interactions, their cellular distribution, and their ligand in adhesive interactions. The family members shown here are limited to those that participate in inflammation and other innate immune mechanisms. The same molecules and others participate in adaptive immunity and will be considered in Chapters 9 and 11. The nomenclature of the different molecules in these families is confusing because it often reflects the way in which the molecules were first identified rather than their related structural characteristics. Alternative names for each of the adhesion molecules are given in parentheses. Sulfated sialyl-LewisX, which is recognized by Pand E-selectin, is an oligosaccharide present on the cell-surface glycoproteins of circulating leukocytes.