Modulation of the migration and chemotaxis of PMN cells by hyaluronic acid.

Hyaluronic acid (HA) has a dose-related inhibiting effect on the migration and chemotaxis of polymorphonuclear leucocytes (PMN) in vitro. These effects were measured with a new indirect quantitative assay. On average 1 mg HA/ml causes an inhibition to about 80% of the control (spontaneous migration). This effect increased progressively with an increasing HA concentration, and with 4 mg HA/ml only about 19% of the PMN were able to migrate in the in vitro system. Similar results were obtained in the presence of a potent chemotactic factor (leukotriene B4 [LTB4]). In the mean 1 ng LTB4/ml alone stimulated the chemotaxis of PMN by a factor of 3 compared to the spontaneous migration. The highest HA concentration (4 mg/ml) reduced the number of migrating PMN cells to about 17%. From these experiments it may be concluded that the HA in the synovial fluid of the healthy joint has a protective effect against the invasion of PMN cells. This functions is disturbed in inflamed joints by the decrease in the HA concentration and possibly by its depolymerization. The intraarticular application of high molecular weight HA might be an important therapeutic regimen to restore the natural barrier against PMN migration, also in the presence of chemotactic factors and could therefore be helpful for interrupting the inflammatory cascade.