CCR7 Ligands Induce Endocytosis and the Formation of Actin-Filled Ruffles in Mature Dendritic Cells

Abstract

We have previously demonstrated that the CCR7 ligands, CCL19 and CCL21, rapidly induce vigorous endocytosis in mature murine dendritic cells (DCs). The mechanisms underlying the enhanced endocytosis, however, have remained elusive. In the present study, we examined effects of CCL19 and CCL21 on the organization of the actin cytoskeleton in murine DCs. These chemokines considerably increased the intracellular level of fibrous actin and induced the formation of large petal-like ruffles of actin filaments in mature DCs. In addition, a robust network of interconnected ruffles of actin filaments was assembled at the periphery of the cells after stimulation with the chemokines. The actin-related protein (Arp) 2/3 complex has been implicated in the formation of fibrous actin structures. During cytoskeletal reorganization, Arp2/3 complexes co-localized with the interconnected ruffles at the cell periphery. Thus, the Arp2/3 complex seems to be involved in CCR7 ligand-induced actin reorganization in mature DCs. The time course of the CCL19-induced actin-reorganization corresponded to that of the endocytic activity. In the presence of cytochalasin D, an actin polymerization inhibitor, CCL19 failed to induce endocytosis and the interconnected ruffles did not form in mature DCs. Thus, CCR7-induced actin assembly may be part of the endocytic process in mature DCs.