Inhibition of ascorbic-acid-induced depolymerization of hyaluronic acid by ceruloplasmin in synovial fluid.

It has been demonstrated in vitro that low concentrations of ascorbic acid rapidly depolymerize purified hyaluronic acid as judged from viscosity measurements (Skanse and Sundblad, 1943; Pigman, Rizvi, and Holley, 1961). Abrams and Sandson (1964) reported that the hyaluronic acid in rheumatoid synovial fluid is resistant to depolymerization by ascorbic acid in vitro. Serum proteins have been shown to inhibit the action of ascorbic acid on purified hyaluronic acid. The alpha-2 globulin fraction was found to contain the serum proteins most active in inhibiting the reaction (De Salegui, Rizvi, Holley, and Pigman, 1962; Pigman and Rizvi, 1959). The increased concentration of blood serum proteins in synovial fluid from patients with rheumatoid arthritis has been repeatedly reported since the original observation of Ropes and Bauer (1953), and the marked increase in alpha-2 globulins has been noted by Binette and Schmid (1965). Reports from this laboratory showed that the concentrations of haptoglobin (Niedermeier, Cross, and Beetham, 1965) and ceruloplasmin (Niedermeier, 1965a), which are both alpha-2 glycoproteins, are markedly raised in synovial fluid of patients with rheumatoid arthritis. Ceruloplasmin has been shown to inhibit ascorbic acid-induced depolymerization of purified preparations of hyaluronic acid (Niedermeier, 1965b, 1966). The present studies were undertaken to determine whether the presence of ceruloplasmin in increased amounts could account for the failure of ascorbic acid to depolymerize hyaluronic acid in synovial fluid from patients with rheumatoid arthritis.