Migration of Dendritic Cells from Blood to Tissues. A fun-damental aspect of dendritic cell (DC) function is their capacity to migrate. It allows them to exert a continuous surveillance for incoming antigens in almost all body tissues and a prompt report to T cells in secondary lymphoid organs. Under steady state conditions, the rate of DC migration from blood to tissues and from tissues to lymph nodes is probably very low, and most of these DCs reside in the tissues in a dormant state ready to be activated by pathogens. However, in inflammatory conditions the rate of DC migration can be considerably increased to meet the increased requirement for antigen presentation. Several recent papers shed new light into the mechanisms that control the various steps that DCs have to undergo to perform their function in the induction of tolerance, priming, and chronic inflammation.

To exit from the blood stream DCs, like other leukocytes, first need to tether to the endothelium (Fig. 1). This process, which is essential for the subsequent steps of firm adhesion and extravasation, is mediated by selectins that bind to specific carbohydrates on specialized cell surface molecules (1). In this issue, Robert et al. demonstrate that DCs that circulate in peripheral blood express a glycosylated form of P-selectin glycoprotein ligand (PSGL)-1 that binds to P-and E-selectins, which are expressed at low levels on endothelial cells and are upregulated by inflammatory stimuli (2). Using an in vivo imaging system, they show that DCs tether and roll on P-and E-selectins expressed by capillary endothelial cells and preferentially extravasate at sites of inflammation. This novel finding indicates that blood-borne DCs are poised to exit blood at inflammatory sites, thus allowing rapid recruitment of these APCs where their surveillance function is most needed. Recruitment of leukocytes from blood to tissues is regulated at the level of the endothelial cells, where inflammatory cytokines increase the expression of adhesion molecules and chemokines and induce the formation of Weibel-Palade bodies. These represent storage granules for P-selectin (3, 4) and, as shown in two recent papers, also for IL-8 (5, 6). The content of the Weibel-Palade bodies can be rapidly mobilized by stimulation of endothelial cells with histamin or thrombin. This mechanism can be viewed as a form of “memory,” since it allows endothelial cells that had been exposed to inflammatory stimuli to respond to a new challenge rapidly and without need for new protein synthesis, which has clear physiological as well as immunopathological significance.