Hyaluronan (hyaluronic acid) and its regulation in human saliva by hyaluronidase and its inhibitors.

The presence of hyaluronan (HA), hyaluronidase and hyaluronidase inhibitors has been assayed in pure resting and stimulated parotid saliva and also in resting and stimulated mixed saliva utilizing an ELISA-type assay and its modifications. Results confirmed the presence of hyaluronan in all saliva specimens which generally decreased upon stimulation. Hyaluronan in parotid saliva was of high molecular weight (> 200,000 kDa) whilst that in whole saliva in the floor of the mouth had a molecular weight between 20,000 kDa and 200,000 kDa, presumably because of cleavage by bacterial hyaluronidases. Hyaluronidase detection was variable in saliva, being present in some specimens of unstimulated parotid saliva, but in fewer specimens of stimulated saliva. Hyaluronidase was detected in parotid and whole saliva, both in the resting and stimulated state, at pH 3.7. Unstimulated whole saliva also showed hyaluronidase activity at pH 6.8, suggesting a different origin for this hyaluronidase. Hyaluronidase inhibitors were identified in both parotid and mixed whole saliva. There was an inverse relationship between the presence of hyaluranidase and the presence of hyluronidase inhibitors, suggesting a feedback mechanism. The possible significance, interactions and function of hyaluronan, hyaluronidase and its regulation by hyaluronidase inhibitors in saliva is discussed, particularly in relation to intra-oral wound healing and periodontal disease.