CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize β1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion
✍ Scribed by Peter Friedl; Frank Entschladen; Christoph Conrad; Bernd Niggemann; Kurt S. Zänker
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 406 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4 + T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of g 1, g 2, or g 3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity g 1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesionperturbing anti-g 1, -g 2, -g 3, and § v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, g 1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin Aactivated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.