**2. Fibrin contributes to the production of MMP-1 and MMP-3 by rheumatoid synovial fibroblasts**

In order to test whether deposition of fibrin might trigger the production of MMPs, we investigated the presence of fibrin in synovial tissues from patients with rheumatoid arthritis. We observed a similar pattern of distribution to those of MMP-1 and -3. These findings led us to explore in vitro whether fibrin could activate the production of MMPs by rheumatoid synovial fibroblasts. In these studies, which we next describe, we introduced an in vitro system that attempts to reproduce the interaction between fibrin and fibroblasts that takes place inside the joint. This model of cell stimulation had originally been developed to study leukocyte migration through vessel walls and is known as in situ fibrin polymerization (Qi & Kreutzer, 1995). In contrast to other types of cultures involving cells and matrix proteins, this approach conserves the shear forces of freshly clotted fibrin networks and exposes cells to the deposits by their apical surface.
