Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines

The function of dendritic cells (DC) depends on active migration through th ree-dimensional (3-D) extracellular matrices. We have analyzed the migratio n of murine DC from different tissue origins within 3-D collagen lattices t hrough the use of time-lapse videomicroscopy and single-cell tracking. Dire ctly after incorporation, 50-90% of DC from the spleen (spDC) and Langerhan s cells freshly isolated from the epidermis (fLC) displayed active motility in these matrices. Whereas mature spDC showed multilateral pseudopod dynam ics as well as fast and heterogeneous migration, immature fLC displayed a s pherical shape with faint membrane processes and very homogenous, slow migr ation characteristics. In the absence of external stimuli, migration of bot h, spDC and fLC, vanished after >36 h due to cell death. Maintaining fLC vi ability by external granulocyte-macrophage colony-stimulating factor or tum or necrosis factor ac prolonged migration up to 5 days, During this period fLC transformed into mature cells with large dendrites, thereby developing a heterogeneous migration pattern more similar to spDC, In randomly polymer ized collagen matrices cell paths were without preferential orientation. In contrast, in artificially aligned lattices directional paths in accordance with the forced fiber orientation were observed. Thus, migration is an inh erent property of DC, largely influenced by tissue origin, degree of maturi ty, and the 3-D structure of the environment.