Figure 8.

Combinatorial regulation of chemotaxis. Leukocyte homing during step-by-step navigation is determined by the combination and sequence of agonists and receptors engaged. In this example, a cell requires receptor a to acquire motile properties and transmigrate through the endothelium in response to agonist A; receptor b to respond to a gradient from an overlapping epithelial surface that draws the cell into the tissue; and receptor c to detect a signal from its end target, and migrate there. Only cells displaying all three receptors can successfully home to the target region. The same receptors and agonists, displayed in different patterns and/or in combination with other receptors, could participate in a variety of different leukocyte targeting scenarios. This schematic emphasizes that simultaneous expression of multiple receptors is required for homing, and demonstrates how receptors that are displayed relatively indiscriminately (by overlapping subsets of leukocytes) can elicit a specific homing pattern when used in combination.