The majority of interactions between a cell and its microenvironment occur through specific cell-surface receptors. Therefore, regulation of receptor function is a critical event for cellular regulation. The most global way of regulating receptor function is by restricting the expression of individual receptors to specific cells of various lineages or to unique stages of differentiation. Expression of the ligand (s) for each receptor may also be limited, thus conferring additional specificity. A second way of regulating receptor function is by limiting the number of receptors expressed per cell. One mechanism for this is receptor internalization following interactions with ligand. The receptor can either be degraded in a specific endosome or, following ligand release, be recycled to the cell surface. A third method for controlling receptor function is by regulating the affinity of a receptor for its ligand, as is the case for some leukocyte adhesion receptors that increase their affinity for ligand following leukocyte activation (1). This affinity change is transient, allowing for adhesive-deadhesive interactions to occur. Thus, after the initial receptor-ligand interactions, the cells are released to interact again with other cells. Recently, a fourth mechanism of cell-surface receptor regulation has been identified. This involves shedding of the receptor from the cell surface following engagement of ligand or activation of the receptor-bearing cell.

A number of surface molecules present on cells of various lineages are now known to be shed and thereby released into the extracellular milieu. These include many of the growth factor receptors, including receptors for interleukin (lL)-I, IL-2 (CD25), transferrin (CD72), insulin, growth hormone, tumor necrosis factor (2), colony-stimulating factor-l (3), and nerve growth factor (4). Also included in this growing list are several immunologically important molecules, including major histocompatibility complex class I and class II antigens, CD8, CDl4, and the adhesion receptor leukocyte adhesion molecule-l (LAM-I)/MEL-I4 (5, 6). Similarly, many of the Fc receptors found on leukocytes are shed, including Fc€ receptor II (CD23), FC'Y receptor II (CD32), and