The chief endothelial cell proteins that are recognized by the white blood cell integrins are called ICAMs (intercellular cell adhesion molecules) or VCAMs (vascular cell adhesion molecules). They are members of another large and ancient family of cell-surface molecules—the immunoglobulin (Ig) superfamily. These contain one or more extracellular Ig-like domains that are characteristic of antibody molecules. They have many functions outside the immune system that are unrelated to immune defenses.
While ICAMs and VCAMs on endothelial cells both mediate heterophilic binding to integrins, many other Ig superfamily members appear to mediate homophilic binding. An example is the neural cell adhesion molecule (NCAM), which is expressed by various cell types, including most nerve cells, and can take different forms, generated by alternative splicing of an RNA transcript produced from a single gene (Figure 19–29). Some forms of NCAM carry an unusually large
Figure 19–28 The structure and function of selectins. (a) the structure of p-selectin. the selectin attaches to the actin cytoskeleton through adaptor proteins that are still poorly characterized. (B) how selectins and integrins mediate the cell–cell adhesions required for a white blood cell to migrate out of the bloodstream into a tissue. First, selectins on endothelial cells bind to oligosaccharides on the white blood cell, so that it becomes loosely attached and rolls along the vessel wall. then the white blood cell activates a cell-surface integrin called LFa1, which binds to a protein called ICaM1 (belonging to the Ig superfamily) on the membrane of the endothelial cell. the white blood cell adheres to the vessel wall and then crawls out of the vessel by a process that requires another immunoglobulin superfamily member called pECaM1 (or CD31), not shown (Movie 19.2). EGF, epidermal  growth factor.
quantity of sialic acid (with chains containing hundreds of repeating sialic acid units). By virtue of their negative charge, the long polysialic acid chains can interfere with cell adhesion (because like charges repel one another); thus, these forms of NCAM can serve to inhibit adhesion, rather than cause it.
A cell of a given type generally uses an assortment of different adhesion proteins to interact with other cells, just as each cell uses an assortment of different receptors to respond to the many soluble extracellular signal molecules in its environment. Although cadherins and Ig superfamily members are frequently expressed on the same cells, the adhesions mediated by cadherins are much stronger, and they are largely responsible for holding cells together, segregating cell collectives into discrete tissues, and maintaining tissue integrity. Molecules such as NCAM seem to contribute more to the fine-tuning of these adhesive interactions during development and regeneration, playing a part in various specialized adhesive phenomena, such as that discussed for blood cells and endothelial cells. Thus, while mutant mice that lack N-cadherin die early in development, those that lack NCAM develop relatively normally but show some mild abnormalities in the development of certain specific tissues, including parts of the nervous system.
In epithelia, as well as in some other types of tissue, cells are directly attached to one another through strong cell–cell adhesions, mediated by transmembrane proteins called cadherins, which are anchored intracellularly to the cytoskeleton. Cadherins generally bind to one another homophilically: the head of one cadherin molecule binds to the head of a similar cadherin on an opposite cell. This selectivity enables mixed populations of cells of different types to sort out from one another according to the specific cadherins they express, and it helps to control cell rearrangements during development.