Effects of hyaluronic acid on macrophage phagocytosis and active oxygen release

The effects of hyaluronic acid (HA) on macrophage function, in terms of the phagocytosis of latex beads and superoxide anion and hydrogen peroxide release stimulated by phorbol myristate acetate (PMA), were studied in guinea-pig peritoneal macrophages. Phagocytosis was inhibited in a dose- and molecular-weight-dependent manner by HA. The addition of PMA to the culture, at a dose of more than 10 ng ml-1, caused an increase in the release of active oxygens. The release of active oxygens was inhibited by high molecular weight HA (MW 2.02 x 10(6), HA-202) in a dose-dependent manner. In cell-free systems, HA-202 had a negligible effect in scavenging these active oxygens. Of the three molecular sizes of HA (MW: 0.28 x 10(6), 0.98 x 10(6) and 2.02 x 10(6)), HA-202 most strongly inhibited the active oxygen release. These results indicate that high-molecular-weight HA acts directly on macrophages to inhibit phagocytosis and active oxygen formation, which, in turn, ameliorates the progression of chronic inflammation.