ABSTRACT
Unlike blood or the digestive tract, proteolytic enzymes in the interstitial space function within a matrix consisting of collagen, other proteins such as vitronectin and fibronectin, and sulfated proteoglycans such as syndecan and chondroitin sulfate. The macromolecules have the potential to modulate the activity of various proteases, as described in subsequent chapters on various groups of proteases. For example, vitronectin accelerates the inactivation of thrombin by plasminogen activator inhibitor-1 (PAI-1) by several orders of magnitude. 1 The activation of plasminogen to plasmin by urokinase-type plasminogen activator (uPA) is slightly enhanced by the extracellular matrix (ECM). 2 Subsequent work from this group 3 showed that collagen I was most effective in stimulating plasminogen activation by uPA, while collagen IV and vitronectin were less effective; inhibition of uPA activation of plasminogen was observed with fibronectin and laminin. Collagen IV is a unique component of basement membrane (BM), while laminin is a major component (Section 2.3). Moser and coworkers 3 did report that uPA bound to vitronectin with higher affinity than that observed for the other ECM components. There is a paucity of studies on the effect of the ECM or ECM components on proteolytic activity in the interstitial space and there are few studies other than that of Moser and coworkers that have solid kinetic data. Such studies are needed to determine the effect of such interactions on interstitial physiology.
