HIGH-MOLECULAR-WEIGHT HYALURONIC ACIDS INHIBIT CHEMOTAXIS AND PHAGOCYTOSIS BUT NOT LYSOSOMAL-ENZYME RELEASE INDUCED BY RECEPTOR-MEDIATED STIMULATIONS IN GUINEA-PIG PHAGOCYTES

The effects of high-molecular-weight (HMW) hyaluronic acids (HAs) of 1.9x10(6) Da, 8x10(5) Da and 3x10(5) Da on the receptor-mediated functions of guinea pig peritoneal phagocytes were studied. HMW-HAs of 1.9x10(6) Da (HA190) and 8x10(5) Da (HA80) effectively inhibited the chemotactic activity of polymorphonuclear leukocytes (PMNs) for formyl-Met-Leu-Phe (fMLP). The degree of inhibition was dose-dependent and the concentrations of HA190 and HA80 required for 50% inhibition were 0.5-1.5 mg/ml and 1.5-2.5 mg/ml, respectively. HMW-HA of 3x10(5) Da (HA30) hardly affected the chemotaxis within a concentration range of 0.5-5.0 mg/ml. The phagocytic activities of PMNs and macrophages (M(phi)s) for serum-opsonized zymosan (SOZ) and polystyrene latex particles were also inhibited by these HAs in a dose- and molecular-weight-dependent manner and HA190 was again the most inhibitory. By contrast, the release of lysosomal enzyme from M(phi)s stimulated with SOZ was not significantly affected by HMW-HAs at any concentration used. Furthermore, the binding of [H-3]fMLP with PMNs and the rosette formation of M(phi)s with SOZ were not influenced by the presence of HMW-HAs. These findings suggested that the binding of HMW-HAs to the HA receptors on PMNs and M(phi)s might produce certain intracellular signals which would be responsible for the suppression of the chemotaxis and the phagocytosis but not for the release of lysosomal enzyme. For the generation of such signals, higher-molecular-weight HMW-HAs would be more effective than lower one.