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 plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) has been demonstrated in bovine milk. 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.


METHODS
Milk samples were separated into the following 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 zymography. The distribution of t-PA and u-PA was investigated by ligand binding analysis. t-PA-catalyzed plasminogen activation was examined by a coupled chromogenic assay.


RESULTS
A differential distribution of plasminogen, t-PA, 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, human casein enhanced t-PA-catalyzed plasminogen activation, comparable to the enhancing effect obtained with fibrinogen fragments.


CONCLUSIONS
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.
Heegaard
C W
CW
Department of Molecular and Structural Biology, University of Aarhus, Denmark.
Larsen
L B
LB
Rasmussen
L K
LK
Højberg
K E
KE
Petersen
T E
TE
Andreasen
P A
PA
D002364:Caseins / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D007457:Iodine Radioisotopes; D008895:Milk, Human / Q000737:chemistry*; D010958:Plasminogen / Q000032:analysis* / Q000276:immunology; D010960:Plasminogen Activators / Q000032:analysis* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism*
D002364:Caseins; D007457:Iodine Radioisotopes; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator