Plasminogen-activator11/9/2022 ![]() Thus, t-PA is believed to be the physiological vascular activator primarily active in fibrinolysis and thrombolysis while bound to fibrin surfaces, whereas u-PA bound to its cell-surface receptor, u-PAR, appears to provide pericellular proteolysis during cell migration and tissue remodeling (1-4).Ī number of observations suggest that the components of the plasminogen activation system have important physiological functions in the mammary gland. This is due to distinct targeting determinants in the noncatalytic domains of t-PA and u-PA localizing the two activators to different surfaces. Despite the resemblance in the catalytic action of the plasminogen activators, they participate in separate physiological and pathological processes. The primary physiological inhibitor of the two plasminogen activators is type-1 plasminogen activator inhibitor (PAI-1), which restricts plasminogen activator activity and thereby delimits the local rate of plasmin generation. Plasmin generation is catalyzed by either of two serine proteinases encoded by different genes, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA). Plasminogen, the inactive zymogen form of the potent serine proteinase plasmin, has been implicated in numerous physiological and pathological processes. The finding of a differential distribution of u-PA and t-PA in milk suggests that the two activators may have different physiological functions, which involve protection against invading microorganisms and maintenance of patency and fluidity in the ducts of mammary gland, respectively. Furthermore, human casein enhanced t-PA-catalyzed plasminogen activation, comparable to the enhancing effect obtained with fibrinogen fragments. Casein micelles were found to exhibit t-PA and plasminogen binding activity, whereas the u-PA receptor was identified as the u-PA binding component in the cell fraction. ResultsĪ differential distribution of plasminogen, t-PA, and u-PA was found. t-PA-catalyzed plasminogen activation was examined by a coupled chromogenic assay. The distribution of t-PA and u-PA was investigated by ligand binding analysis. The different fractions were detected for the presence of plasminogen and plasminogen activators by immunoblotting and zymography. Milk samples were separated into the following fractions milk fat, skim milk, and milk cells by centrifugation. To assess whether this distribution pattern is a general feature, the occurrence of components of the plasminogen activation system in different fractions of human milk was investigated. Recently, a differential distribution of tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) has been demonstrated in bovine milk. The level of plasmin activity is controlled by the availability of the precursor plasminogen and by the levels of plasminogen activators and inhibitors. Plasmin is the major endogenous protease present in milk. ![]()
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