Plasminogen activators and their inhibitors in human saliva and salivary gland tissue

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Abstract
The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell‐free saliva and to investigate their expression in salivary gland tissue. Saliva samples were obtained from 34 patients visiting a neurological out‐patient department. The activities of tissue and urokinase plasminogen activators (tPA and uPA, respectively), the relative inhibition of tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI‐1 and PAI‐2, respectively) in cell‐free saliva were studied. The activities of tPA and uPA, and tPA inhibition, were measured using in‐house microtiter plate assays, and PAI‐1 and PAI‐2 levels were measured using commercial enzyme‐linked immunosorbent assay (ELISA) kits. Immunohistochemistry was used to evaluate the expression of PAs and PAIs in the salivary gland. Tissue plasminogen activator activity was found in most samples, with a mean activity of 0.63 IU ml−1. uPA was observed in only a few samples. PAI‐1 was not detected, but PAI‐2 was present in all samples (with a mean value of 11.1 ng ml−1). The mean PAI‐2 level in women was 12.4 and in men was 7.6 ngml−1. The activity of tPA and the relative inhibition of tPA seemed to be inversely associated. Tissue plasminogen activator, PAI‐1, and PAI‐2 were evident in salivary gland tissue, whereas the expression of uPA was low. The tPA activity in saliva suggests an active proteolysis. Plasminogen activator inhibitor 2 was found to be the main inhibitor of PAs in saliva.