PLASMINOGEN ACTIVATION SYSTEM IN HUMAN-MILK

Background: Plasmin is the major endogenous protease present in milk. The level of plasmin activity is controlled by the availability of the precursor plasminogen and by the levels of plasminogen activators and inhibitors. Recently, a differential distribution of tissue-type plas minogen activator (t-PA) and urokinase-type plasminogen activator (u-P A) has been demonstrated in bovine milk. To assess whether this distri bution pattern is a general feature, the occurrence of components of t he plasminogen activation system in different fractions of human milk was investigated. Methods: Milk samples were separated into the follow ing fractions; milk fat, skim milk, and milk cells by centrifugation. The different fractions were detected for the presence of plasminogen and plasminogen activators by immunoblotting and zy mography. The dist ribution of t-PA and u-PA was investigated by ligand binding analysis. t-PA-catalyzed plasminogen activation was examined by a coupled chrom ogenic assay. Results: A differential distribution of plasminogen, t-P A, and u-PA was found. 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. Furthermore, huma n casein enhanced t-PA-catalyzed plasminogen activation, comparable to the enhancing effect obtained with fibrinogen fragments. Conclusion: The finding of a differential distribution of u-PA and t-PA in milk su ggests that the two activators may have different physiological functi ons, which involve protection against invading microorganisms and main tenance of patency and fluidity in the ducts of mammary gland, respect ively.