Receptor‐mediated binding of leukocyte elastase by chondrocytes

Abstract

Studies on the effect of leukocyte elastase on the metaboliSm of chondrocytes in culture have demonstrated that these cells possess a specific cell surface receptor for leukocyte-derived elastase. Purified elastase from rabbit and human leukocytes is capable of modulating the metabolism of the cell by causing a marked decrease in both proteoglycan and protein biosynthesis. Addition of '251-labeled elastase to chondrocytes maintained in suspension culture has shown that binding occurs, and that it is saturable and is inhibited by the addition of unlabeled enzyme. We ascertained that the active site of the enzyme was necessary for binding to the chondrocyte, since phenylmethylsulfonyl fluoriib inactivated leukocyte elastase failed to bind. Pancreatic elastase had only a slight afiinity for the receptof, whereas trypsin and bovine serum albumin failed to bind to any significant extent. Autoradiographic studies and the use of inhibitors of endocytosis, such as dansyl cadaverine, confirmed that endocytosis of elastase was the secondary event after cell binding.The characteristic features of chronic inflammatory arthritis include the formation of an invasive pannus, the result of synovial cell proliferation cou-

Immunocytochemical evidence for extra-cellular initiation of elastase-induced bronchial secretory cell metaplasia in hamsters

“…Uptake by alveolar macrophages has been shown to be receptor-mediated [20]. Receptors for elastase uptake are also present on neutrophils [21], and cultured chondrocytes [22]. Whilst our results do not exclude the possible presence of elastase receptors on airway epithelial cells, they argue against receptor-mediated uptake of elastase.…”

ICAM-1 Signal Transduction in Cells Stimulated with Neutrophil Elastase

“…Neutrophil elastase interacts with a cell surface receptor on mononuclear phagocytes [36,37], and induces the release of glycoconjugates and surface macromolecules by bronchoepithelial cells [38,39]. The active site of elastase may be required for the receptor-mediated binding of leukocyte elastase to chondrocytes [40]. This binding may be required for the signal transduction pathway responsible for neutrophil elastase-induced ICAM-1 gene expression in endothelial cells.…”

High resistance of the mechanical properties of the chondrocyte pericellular matrix to proteoglycan digestion by chondroitinase, aggrecanase, or hyaluronidase

“…Elevated levels of elastase are present in the synovial fluid of patients with rheumatoid arthritis (Elsaid et al, 2003; Ishiguro et al, 2001; Momohara et al, 1997), osteoarthritis (Elsaid et al, 2003; Momohara et al, 1997), and following acute joint injury (Elsaid et al, 2008; Elsaid et al, 2003). In addition to binding to the articular surface (Janoff et al, 1976; Kawabata et al, 1996), elastase is capable of diffusing through the cartilage matrix (Janoff et al, 1976) and binding to chondrocytes in a receptor-mediated manner (Bartholomew and Lowther, 1987; Menninger et al, 1981). These properties provide a means and potential mechanism for localization of elastase to PCM regions.…”