Specificity of leukocyte-endothelial interactions and diapedesis: physiologic and therapeutic implications of an active decision process.

In situ studies have revealed that an active multistep process regulates leukocyte-endothelial cell recognition and diapedesis in vivo. The requirement for sequential engagement of receptors mediating transient adhesion, leukocyte activation, activation-dependent sticking and diapedesis implies that leukocyte recruitment can be regulated at any of these 4 steps, and provides a combinatorial mechanism to explain the remarkable specificity and diversity of leukocyte homing events in vivo. The model will help direct therapeutic approaches to controlling leukocyte traffic.