Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1

Inflammatory processes are associated with the rapid migration of dendritic cells (DCs) to regional lymph nodes and depletion of these potent antigen-presenting cells (APCs) from the Inflamed tissue. This study examined whether sites of cutaneous Inflammation can be repopulated with DCs from a pool of Immature DCs circulating In the blood. In adoptive transfer experiments with ex vivo-generated radioactively labeled primary bone marrow-derived DCs Injected into mice challenged by an allergic contact dermatitus reaction, Immature DCs were actively recruited from the blood to sites of cutaneous Inflammation, whereas mature DCs were not. Immature, but not mature, DCs were able to adhere specifically to immobilized recombinant E- and P-selectin under static as well as under flow conditions. P-selectin-dependent adhesion of immature DCs correlates with their higher level of expression of the carbohydrate epitope cutaneous lymphocyte-associated antigen (CLA) and is blocked by a novel Inhibitory antibody against mouse P-selectin glycoprotein ligand 1 (PSGL-1). Surprisingly, however, emigration of Immature DCs Into Inflamed skin is retained In the presence of this anti-PSGL-1 antibody and is also normal when immature DCs are generated from fucosyltransferase (Fuc-T) Fuc-TVII-deficient mice. By contrast, emigration of wild-type Immature DCs Is reduced by adhesion-blocking anti-E- and P-selectin antibodies, and immature DCs generated ex vivo from Fue-TVII/Fuc-TIV double- deficient mice emigrate poorly. Thus, fucosylated ligands of the endothelial selectins, determined in part by Fuc-TIV, and Independent of PSGIL-1, are required for extravasation of DCs into sites of cutaneous inflammation. (C) 2002 by The American Society of Hematology