Effects of high-molecular-weight hyaluronates on the functions of guinea pig polymorphonuclear leukocytes

The effect of hyaluronate (HA) with a molecular weight of 1,900,000 (HA190) purified from products of Streptococcus equi on various functions of guinea pig peritoneal polymorphonuclear leukocytes (PMNs) was examined. HA190 effectively inhibited both the chemotactic activity of PMNs for a chemotactic peptide, formyl-Met-Leu-Phe, and the phagocytic activity of the cells for serumopsonized zymosan (SOZ) in a dose-dependent manner. When the inhibitory activity of the HAs of different molecular weights, including HA190, HA of molecular weight 800,000 (HA80), and HA of molecular weight 300,000 (HA30), was assessed, the HA190 showed the strongest inhibitory activity and HA30 the lowest activity. In contrast, significant inhibition of the superoxide generation by PMNs upon stimulation with SOZ was not observed even in the presence of HA190 and HA80 at the highest concentration used (2.5 mg/mL). This finding indicated that the HAs studied did not prevent the interaction of PMNs with stimuli. From these data it is concluded that the binding of high-molecular-weight HAs to the HA receptors on PMNs may produce intracellular signals that are responsible for suppression of phagocytosis and Chemotaxis but not for superoxide generation.