Extracellular matrix‐cytoskeletal interactions in rheumatoid arthritis. I. Immunoelectron microscopic analysis of the fibronexus at the adhesive surface of normal porcine type B synoviocytes in vitro

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Abstract
We studied cell surface interactions between the fibronectin (FN)‐containing extracellular matrix and the actin cytoskeleton of normal porcine synoviocytes in vitro, using electron microscopic methods. These type B synovial cells were distinguishable from dermal fibroblasts co‐isolated from the same organism, because of their very long cellular processes and their ability to synthesize prostaglandin E2 after stimulation with interleukin‐1. With plastic sections, we found end‐to‐end (tandem) and track‐like (lateral) transmembrane associations of extracellular fibers and cortical 5‐nm microfilaments localized along the attenuated synoviocyte processes in postconfluent cultures. Very similar FN–actin complexes, termed fibronexus (FNX), have been observed on cultured fibroblasts and on granulation tissue myofibroblasts in vivo. Using double‐label immunoelectron microscopy with monospecific antibodies applied to ultrathin frozen sections of synoviocytes cut in situ, we proved that these FNX were indeed composed of associated FN and actin filaments. The striking finding of numerous FNX in cultured type B synoviocytes strongly suggests that the FNX is a major cell surface adhesion site in normal synovium, which may play an important role in pannus formation, connective tissue remodeling, and synoviocyte proliferation in patients with rheumatoid arthritis.