Urokinase-type plasminogen activator inhibits α4β1 integrin-mediated T lymphocyte adhesion to fibronectin independently of its catalytic activity
✍ Scribed by Philippe Olivier; Grégory Bieler; Kai M. Müller; Dan Hauzenberger; Curzio Rüegg
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 246 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
The urokinase-type plasminogen activator (u-PA)/plasmin system plays an important role in promoting cell migration and invasion, an effect which is largely ascribed to the proteolytic activity of these enzymes. We investigated whether u-PA modulates integrin-dependent T lymphocyte migration and adhesion on fibronectin independently of its plasminogen activator function. Here we report that u-PA reduced the spontaneous and phorbol 12-myristate 13-acetate-induced migration of peripheral blood T lymphocytes on fibronectin by 20-50 %, decreased the T lymphocyte and § 4 g 1 + / § 5 g 1 + K562 cell adhesion on fibronectin by 30-40 %, and completely suppressed integrin § 4 g 1-dependent T lymphocyte and § 4 g 1 + / § 5 g 1 + K562 cell adhesion to the LDV-containing 40-kDa fibronectin fragment. The u-PA receptor was not essential for this effect. In contrast, adhesion of § 4 g 1 -/ § 5 g 1 + K562 cells to an RGD-containing fibronectin fragment was unaffected. A recombinant protein comprising the N-terminal fragment of u-PA, but lacking its proteolytic domain, had the same inhibitory effect. Decreased adhesion was neither associated with a diminished cell surface expression of § 4 g 1 nor with a suppression of § 4 g 1 ligand-binding function. Our results demonstrate that u-PA inhibits § 4 g 1-but not § 5 g 1-mediated lymphocyte/leukocyte adhesion to fibronectin independently of its proteolytic activity. This finding provides additional evidence that matrix proteinases may participate in cell adhesion and migration control independently of their matrix-degrading activity.