Plasminogen activators and plasminogen activator inhibitors in synovial fluid. Difference between inflammatory joint disorders and osteoarthritis

The plasminogen activator (PA)/plasminogen activator inhibitor (PAI) system is believed to be involved in connective tissue remodelling in joint disease and both PA and PAI production has been shown in several cell types in the joint. We quantified immunoreactive PA and PAI in synovial fluid (SF) and correlated their levels to levels of cartilage derived proteoglycans, radiologically visible joint involvement and to signs of local inflammation. PAI-2 concentrations were increased, compared to normal plasma levels, in patients with rheumatoid arthritis (RA) and reactive arthritis, but not in patients with osteoarthritis (OA). Thirty percent of the patients with RA, but no patient with OA had increased concentrations of PAI-1. Increased concentrations of urokinase type PA (u-PA) were found in RA but not in OA. Tissue type PA (t-PA) concentrations were low in both disease groups. SF proteoglycan concentrations did not correlate with levels of PA or PAI. Concentrations of PAI-2 correlated significantly with SF leukocyte count and cytidine deaminase (CD) activity and u-PA concentrations correlated with CD activity. Both PAI-2 and u-PA were detected in supernatants from lysed polymorphonuclear cells. This suggests that in addition to release from synovial cells and chondrocytes these components may also be released from polymorphonuclear cells. Our results support a pathophysiological role for the fibrinolytic system in joint disease, possibly more pronounced in inflammatory disorders than in OA

Increasing expression of tissue plasminogen activator and plasminogen activator inhibitor type 2 in dog gingival tissues with progressive inflammation

Urokinase and tissue-type plasminogen activators (u-PA and t-PA) are serine proteases that convert plasminogen into plasmin, which degrades matrix proteins and activates metalloproteinases. The PAs are balanced by specific inhibitors (PAI-1 and PAI-2). Local production of t-PA and PAI-2 was recently demonstrated in human gingival tissues. The aim now was to investigate the production and localization of t-PA and PAI-2 in gingival tissues from dogs in three well-defined periodontal conditions; clinically healthy gingiva, chronic gingivitis and an initial stage of ligature-induced loss of attachment. At the start of the experiment the gingiva showed clear signs of inflammation. Clinically healthy gingiva were obtained after 21 days period of intense oral hygiene. Attachment loss was induced by placing rubber ligatures around the neck of some teeth. Biopsies were taken from areas representing the different conditions and prepared for in situ hybridization and immunohistochemistry. In clinically healthy gingiva both t-PA mRNA and antigen were expressed in a thin outer layer of the sulcular and junctional epithelia. No t-PA signals or staining were seen in connective tissue. Both mRNA signaling and immunostaining for t-PA were stronger in chronic gingivitis. In areas with loss of attachment, t-PA mRNA as well as antigen were found in the sulcular and junctional epithelia to a similar degree as in gingivitis. Occasionally the connective tissue was involved, especially in connection with vessels. PAI-2 mRNA was seen in a thin outer layer of the sulcular and junctional epithelia in clinically healthy gingiva, but no signals were seen in connective tissue. PAI-2 antigen was found primarily in the outer layer of the sulcular and junctional epithelia. Some cells in the connective tissue were stained. In gingivitis, PAI-2 signals were mainly found in the same locations, but more intense and extending towards the connective tissue. Immunostaining was seen in the outer half of the sulcular and junctional epithelia as well as in the upper part of the connective tissue, close to the sulcular epithelium. In sites with loss of attachment, PAI-2 mRNA was found throughout the sulcular and junctional epithelia, as was the antigen, which stained intensely. No PAI-2 mRNA was seen in connective tissue; the antigen was found scattered, especially near vessels. This study shows that the expression of both t-PA and PAI-2 increases with experimental gingival inflammation in the dog, and furthermore, the two techniques demonstrate a strong correlation between the topographical distribution of the site of protein synthesis and the tissue location of the antigens for both t-PA and PIA-2. The distribution correlates well with previous findings in humans. © 2000 Elsevier Science Ltd.link_to_subscribed_fulltex

Variations in fibrinolytic activity of human whole saliva

The physiological variations of fibrinolytic activity (FA) in saliva were investigated in a population of 149 healthy volunteers including 12 pregnant women. An increase in FA could be observed with increasing age. Marked variations were observed during daytime with a peak value early in the morning. Higher FA values were observed in males as compared with females in the 20-39 yr age group. A clear decrease in FA was observed during pregnancy. A significant correlation existed between FA and suspended epithelial cell concentration, which seemed responsible for most of the physiological FA variations. It was concluded that age, sex, pregnancy, and the time of the day are important for salivary FA and should be taken into account in any study on salivary FA related to physiological or pathological processes. © Munksgaard, 1996.SCOPUS: ar.jSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe