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PubMed1993

Comparison of the lysine binding functions of lipoprotein(a) and plasminogen.

Regions of apoprotein(a) of lipoprotein(a) [Lp(a)] exhibit striking primary sequence homology to the kringles of plasminogen. The kringles of plasminogen are lysine binding structures and mediate interactions of plasmin(ogen) with substrates and inhibitors. In the current study, the lysine binding properties of Lp(a) have been compared to those of plasminogen and isolated kringle 4 of plasminogen (K4). An analytical assay was implemented to quantitate the interaction of kringle-containing molecules with lysine-Sepharose beads. Radioiodinated ligands, Lp(a), plasminogen, and K4, bound to the beads, and their interactions were inhibited by lysine analogues in a dose-dependent fashion. A series of omega-aminocarboxylic acids inhibited Lp(a), plasminogen, and K4 binding to the lysine-Sepharose beads, but marked differences in the effectiveness of these compounds were observed with each ligand. In this series of compounds, 6-aminohexanoic acid was the most potent inhibitor of binding to lysine-Sepharose for all three ligands. The pH had little effect on the inhibition of plasminogen binding by these compounds. For Lp(a), a low pH caused a marked decrease in inhibition by the 5-carbon and 4-carbon omega-amino acids. In addition, tranexamic acid was 750-fold more potent than lysine in inhibiting plasminogen and 55-fold more potent for K4 binding to the beads. In contrast, the differential potency of these compounds on Lp(a) binding was only 3-fold. These results suggest that the kringles of Lp(a) possess lysine binding functions which are similar, but not identical, to those of plasminogen and its K4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1983

Location of plasminogen-binding sites in human fibrin(ogen).

Affinity chromatography of various fibrinogen and fibrin fragments on Lys-plasminogen-Sepharose was used to localize the plasminogen-binding sites in human fibrin(ogen). The fragments studied in the present investigation were derived from the central (E) and the terminal (D) globular domains of fibrinogen and fibrin. Our results showed that these two different, sequentially nonidentical domains of fibrin(ogen) both carry plasminogen-binding sites. Competitive affinity chromatography of fragment D1 and fragments derived from it by proteolytic modification of its D gamma-chain revealed that this modification causes an 11-fold increase of the association constant of the interaction with Lys-plasminogen-Sepharose. This suggests that the carboxy-terminal region of the D gamma-chain is involved in controlling the plasminogen-binding site of the D domain. In contrast with its fragments, intact fibrinogen is not retained by Lys-plasminogen-Sepharose, indicating that the plasminogen-binding sites present in the constituent E and D domains are not fully functional in the parent molecule. It seems possible that the plasminogen-binding sites are present but hidden in fibrinogen and proteolytic dissection of the molecule uncovers these sites in E and D fragments by removing peptides masking the plasminogen-binding regions.

Binding Sites↗
PubMed1987

Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen.

Apolipoprotein(a) [apo(a)] is a glycoprotein with Mr approximately equal to 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from two tryptic fragments show homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain.

Amino Acid Sequence↗
PubMed1988

Discrepant changes in plasminogen by two different assays in patients receiving streptokinase.

The fluorogenic synthetic substrate and radial immunodiffusion assays of plasma plasminogen were compared before and after administration of intravenous streptokinase in differing doses to 57 patients being treated for acute myocardial infarction. There was a moderate correlation (r = 0.73, slope = 0.221, intercept = 1.005, n = 57 pairs) in the two assays of plasma plasminogen before the administration of streptokinase. After streptokinase, however, the correlation of the two assays was poor (r = 0.28, slope = 0.03, y-intercept = 0.003, n = 57 pairs). The decrease in plasma plasminogen by the fluorogenic synthetic substrate assay after streptokinase averaged 95 +/- 5%, with little variation between doses. In contrast, the percentage decrease in plasma plasminogen after streptokinase by the radial immunodiffusion assay averaged only 30 +/- 11%. The percentage change in plasma plasminogen by the two assays is significantly different (P = 0.001). The discrepancy in the percentage change in plasma plasminogen after streptokinase as measured by the fluorogenic synthetic substrate assay and the radial immunodiffusion assay can be explained by a lack of specificity for the antibody to plasminogen in the radial immunodiffusion kit. Antigen-antibody precipitin rings were observed after incubation of antibody with a mixture presumed to contain plasmin, plasmin-alpha 2 antiplasmin complexes, and plasmin-fibrin/fibrinogen degradation products. Based on these data, the fluorogenic synthetic substrate assay for plasma plasminogen is a superior means of following plasminogen depletion in response to thrombolytic therapy after streptokinase treatment for acute myocardial infarction.

Dose-Response Relationship, Drug↗
PubMed1994

Kinetic studies on the plasminogen activation by the staphylokinase-plasmin complex.

A pure complex of staphylokinase and plasmin was prepared by affinity chromatography with lysine-Sepharose, which enabled the simple analysis of the mechanism of plasminogen activation by staphylokinase. We used a truncated staphylokinase (SAK), which lacks the 10 amino acid residues at the NH2 terminal of native staphylokinase. The purity of this complex was confirmed by the native PAGE profile. Image analysis of the SDS-PAGE profile revealed that the molar ratio of plasmin and SAK in the complex was about 1:1. Using this SAK-plasmin complex, the kinetic parameters for the activation of Glu- or Lys-plasminogen were determined. The kinetic constant, kcat/Km, obtained when Lys-plasminogen was used as a substrate was approximately 10 times higher than that obtained when Glu-plasminogen was used. This plasminogen activation property of the SAK-plasmin complex was comparable to that of other plasminogen activators, such as streptokinase, urokinase, and tissue-type plasminogen activator (t-PA). This SAK-plasmin complex will simplify the elucidation of plasminogen activation by SAK. Through kinetic studies, the fibrin specificity and participation of plasminogen activator inhibitor will be clarified.

Fibrinolysin↗
PubMed2004

A central role for plasminogen in the inflammatory response to biomaterials.

The inflammatory response to implanted biomaterials severely limits their deployment in patients. Plasminogen has been shown to play a central role in cell migration, and therefore could regulate this inflammatory response. We sought to determine if plasminogen influences recruitment of inflammatory cells to a biomaterial implanted into plasminogen-deficient (Plg(-/-)) mice. Small disks of polyethylene terephthalate, a material used in vascular grafts, were surgically implanted into the peritoneum of wild-type and Plg(-/-) mice. Recruitment of neutrophils and monocytes/macrophages into the peritoneum and onto the disks was measured, primarily at 18 h. Monocyte/macrophage recruitment was markedly blunted in Plg(-/-) mice compared with wild-type mice. Unexpectedly, neutrophil recruitment was also markedly decreased in the Plg(-/-) mice. While recruitment of leukocytes into the peritoneum was plasminogen-dependent, the adhesion of the emigrating cells to the implants was not. In contrast, adhesion but not recruitment was reduced in fibrinogen-deficient mice. Reconstitution of Plg(-/-) mice with intravenous or intraperitoneal plasminogen differentially restored monocyte/macrophage and neutrophil recruitment. Tranexamic acid, an inhibitor of the lysine binding sites of plasminogen, suppressed leukocyte recruitment in wild-type mice, but aprotinin, a plasmin inhibitor, did not. Plasminogen exerts a marked influence on both neutrophil and monocyte/macrophage recruitment to implanted biomaterials. This role is distinct from that of fibrinogen, and the two inflammatory cell types use plasminogen in different ways. Plasminogen represents a therapeutic target for controlling the inflammatory response to implanted materials.

Animals↗
PubMed1983

Uptake of 125I-Lys-plasminogen by in vitro thrombi.

The specificity, distribution and rate of uptake of radiolabelled 125I-Lys-plasminogen by in vitro thrombi was investigated. 125I-Lys-plasminogen was added to whole blood perfusion mediums containing preformed thrombi and to whole blood prior to thrombus formation. Uptake was assessed by means of radioisotopic analysis and autoradiography. The plasminogen was taken up by thrombi during and after their formation. The largest percentage was in the fibrin component. epsilon-Aminocaproic acid-blocking experiments confirmed the specificity of plasminogen binding to fibrin. Autoradiography of the thrombi revealed plasminogen in the RBC-fibrin part and in platelet-fibrin aggregates. Plasminogen uptake and penetration into preformed thrombi were found to increase as a function of time. However, formation of thrombi from plasminogen-enriched blood was a more effective means for increasing the plasminogen content of thrombi than perfusion of preformed thrombi in a plasminogen-enriched medium, over the time period studied.

Autoradiography↗
PubMed1988

Basics and practice in evaluating plasminogen.

There exist different ways of assays of plasminogen which give information about different properties of this proenzyme. The concentration of plasminogen can be determined by its antigenicity. Since the normal concentration of plasminogen in plasma is between 15 and 25 mg/dl the test can be carried out by simple methods such as radial immunodiffusion on Partigen plates. The possibility of errors is small and there is no need of special apparatus. The disadvantages are the lapse of 24 h until the result is available and the fact that the knowledge of the concentration does not give any information about the activity. The activity can be measured by different coagulation tests. A typical assay would involve activation of plasminogen to plasmin, addition of plasminogen-free thrombin and measuring of the lysis time. The result is however, dependent on more than one variable. Plasmin is rapidly inhibited by alpha-2-antiplasmin (APL) and there is also a dependence of the lysis time on the amount of clottable fibrinogen in the test system. Better results can be obtained by the use of diluted test plasma and addition of a constant amount of plasminogen-free fibrinogen. A different way would be the use of the euglobulin fraction instead of plasma. This has however, the possible disadvantage of incomplete precipitation of plasminogen. Instead of coagulation tests the activity can also be determined when diluted activated plasma is placed on plasminogen-free fibrin plates and the amount of lysis in the plate is recorded. All assays of this group also depend on the method of activation of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗
PubMed1983

Immunological characterization and possible origin of plasminogen activator in human tear fluid.

Human tear fluid has plasminogen activator activity. The type of plasminogen activator activity in unstimulated and stimulated tears was determined, using antibodies that specifically neutralize tissue plasminogen activator or urokinase. All plasminogen activator activity was tissue plasminogen activator-related in both types of tears. Correlations between activities of beta-hexosaminidase, lysozyme and lactate dehydrogenase with tissue plasminogen activator activity indicate that the contribution to plasminogen activator activity of conjunctival and corneal epithelium is more important in unstimulated tears than stimulated tears. In stimulated tears the tissue plasminogen activator activity originates mainly from the lacrimal gland. It is suggested that a constant concentration of plasminogen activator is released from the lacrimal gland and that this concentration is independent of the secretion rate of tear fluid and that the release from the conjunctiva is due to desquamation of cells.

Adult↗
PubMed1992

Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes.

BACKGROUND AND PURPOSE: Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator. METHODS: Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months. RESULTS: Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type. CONCLUSIONS: Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.

Aged↗
PubMed1993

Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends. METHODS: Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator. RESULTS: Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fisher's Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group. CONCLUSIONS: A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.

Aged↗
PubMed2001

Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II.

Genetic evidence demonstrates the importance of plasminogen activation in the migration of macrophages to sites of injury and inflammation, their removal of necrotic debris, and their clearance of fibrin. These studies identified the plasminogen binding protein annexin II on the surface of macrophages and determined its role in their ability to degrade and migrate through extracellular matrices. Calcium-dependent binding of annexin II to RAW264.7 macrophages was shown using flow cytometry and Western blot analysis of EGTA eluates. Ligand blots demonstrated that annexin II comigrates with one of several proteins in lysates and membranes derived from RAW264.7 macrophages that bind plasminogen. Preincubation of RAW264.7 macrophages with monoclonal anti-annexin II IgG inhibited (35%) their binding of 125I-Lys-plasminogen. Likewise, plasmin binding to human monocyte-derived macrophages and THP-1 monocytes was inhibited (50% and 35%, respectively) when cells were preincubated with anti-annexin II IgG. Inhibition of plasminogen binding to annexin II on RAW264.7 macrophages significantly impaired their ability to activate plasminogen and degrade [3H]-glucosamine-labeled extracellular matrices. The migration of THP-1 monocytes through a porous membrane, in response to monocyte chemotactic protein-1, was blocked when the membranes were coated with extracellular matrix. The addition of plasminogen to the monocytes restored their ability to migrate through the matrix-coated membrane. Preincubation of THP-1 monocytes with anti-annexin II IgG inhibited (60%) their plasminogen-dependent chemotaxis through the extracellular matrix. These studies identify annexin II as a plasminogen binding site on macrophages and indicate an important role for annexin II in their invasive and degradative phenotype.

Animals↗
PubMed1977

Serum plasminogen and lung surfactant in the respiratory distress syndrome.

Plasminogen, total protein, and surface-active material were measured in amniotic fluid in 112 pregnancies at 11-42 weeks' gestation. In 65 of these pregnancies, cord blood was also analyzed for serum plasminogen and total protein. Plasminogen was detected in 25 of 114 amniotic fluid samples, and 23 came from pregnancies of less than 37 weeks' gestation. Plasminogen was found in 15 of 32 amniotic fluid samples from pregnancies with complications, but only in 10 of 80 "uncomplicated" pregnancies. The mean cord serum plasminogen was relatively constant in births or abortuses of 17 to 30 weeks' gestation, but was present in increasing amounts in births of gestational ages from 30 to 40 weeks. The concentration of plasminogen in cord serum was directly related to the cord total protein (r = 0.7513, P less than 0.001). The cord plasminogen concentration was significantly higher in infants with a positive foam stability test (5.6 +/- 0.3 mg/100 ml) than in the combined group of infants with negative and intermediate tests (4.3 +/- 0.16, P less than 0.005). However, infants with a positive foam stability also had a significantly greater gestational age than infants with a negative or intermediate foam stability test. With one exception, infants with a low cord plasminogen (below 4 mg/100 ml) developed respiratory distress syndrome (RDS) only if amniotic fluid surfactant was low. The data suggest that low levels of serum plasminogen are correlated with severe lung disease only in the presence of surfactant deficiency.

Amniotic Fluid↗
PubMed1998

The cleavage of pro-urokinase type plasminogen activator by stromelysin-1.

Membrane binding of urokinase type plasminogen activator (u-PA) is thought to play a pivotal role in connective tissue remodeling and invasive processes. We compare the ability of different matrix-metalloproteinases involved in connective tissue turnover to cleave pro-urokinase type plasminogen activator between the catalytic domain and the receptor binding part to investigate a potential role for matrix-metalloproteinases in the regulation of membrane-associated proteolytic activity. We employed several forms of human stromelysin-1 (full length, C-truncated, and recombinant catalytic domain), rabbit C-truncated stromelysin-1, the human gelatinases A and B and the human catalytic domain of neutrophil collagenase. The gelatinases and the collagenase did not separate the receptor binding domain of pro-urokinase type plasminogen activator from the catalytic domain, whereas all stromelysin-1 forms cleaved the glutamic acid 143-leucine 144 bond of pro-urokinase type plasminogen activator. This reaction could be inhibited by specific inhibitors of matrix metalloproteinases and was not affected by inhibitors of serine proteinases. The M(r) 31000 cleavage product with leucine 144 as N-terminus displayed no proteolytic activity towards the pro-urokinase type plasminogen activator substrate pyroGlu-Gly-Arg-pNA-HCI (S2444), but it could be activated by an additional treatment with plasmin. Comparison between full length stromelysin-1 and its C-truncated forms, showed that both exhibited the same cleavage properties towards pro-urokinase type plasminogen activator. Thus, the cleavage of pro-urokinase type plasminogen activator by stromelysin-1 is not influenced by the presence or absence of the C-terminal domain. The recombinant catalytic domain of MMP-3 generated pro-urokinase type plasminogen activator, whereas incubation of pro-urokinase type plasminogen activator with the native forms of human or rabbit stromelysin-1 led to a moderate activation of pro-uPA due to an additional cleavage that is catalyzed by a serine proteinase.

Animals↗
PubMed1996

Identification of plasminogen in Matrigel and its activation by reconstitution of this basement membrane extract.

Matrigel, a basement membrane (BM) extract of the Engelbreth-Holm-Swarm (EHS) sarcoma, used in tumor invasion assays, was found to contain plasminogen. Plasminogen was identified, using Western blot analysis and casein zymograms, by comparison with human plasminogen. matrigel contained approximately 20-100 ng of plasminogen per 100 micrograms of protein as determined by these assays. Matrigel reconstitution and incubation at 37 degrees C caused activation of plasminogen, which was serine protease dependent and involved tissue plasminogen activator (tPA) as an anti-tPA antibody which inhibited activation. This reconstitution and incubation also caused leupeptin-inhibitable degradation of Matrigel components as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Degradation of the BM extract copolymerized in zymograms was caused by human plasminogen and plasminogen in the Matrigel. Maximal plasmin activity, following incubation of Matrigel at 37 degrees C for 16 h, was equivalent to approximately 10 ng of purified plasmin using the plasmin substrate D-Val-Leu-Lys p-nitroanilide. matrigel, therefore, contained all the components of the plasmin-generating system, including plasminogen. The plasmin generated degraded Matrigel components and exogenous substrates. Our data suggest that, since this tumor BM acts as a reservoir for enzymes of the plasmin-generating system, caution should be taken by investigators interpreting data concerning the effects of Matrigel on cell behavior and, in particular, cellular invasion.

Basement Membrane↗
PubMed2002

Plasminogen activation on the cell surface.

The plasminogen activation system appears to be widely involved in many biological processes in health and disease, but the regulation of plasmin generation or the mechanisms of stimulation by cell surface receptors are not well understood. Cell surface plasminogen activation requires binding sites for plasminogen substrate and activator enzyme before enhancement of plasmin generation rate is observed. The cell surface moieties involved in binding these reactants appear to be a mixed group of proteins and other molecules, many of which have been extensively investigated. The binding of plasminogen in particular is characterized by heterogeneous receptor molecules, present in high number but generally with low affinity for plasminogen. The low affinity of the interaction, with Kd values around 10(-6) M, presents considerable technical difficulties when studying and quantitating plasminogen binding to cells or isolated receptors. Studying plasminogen activation kinetics in the presence of cells also presents technical difficulties and raises difficult questions on interpretation of results. However, approaches developed to study enzyme activation systems in other areas of hemostasis may also be applied to the problems associated with pericellular proteolysis. Models should be developed that match In vitro experimental data and help us understand the meaning of kinetic constants derived from these systems. In this way it should be possible to better understand the regulation of plasminogen activation around the cell under normal conditions and in a variety of disease states where cell-associated plasminogen activation is believed to be up-regulated. Ultimately, a sound understanding of theses regulatory mechanisms will enable us to devise strategies for modulating proteolytic activity, test these approaches in well designed In vitro systems and relate these results to the in vivo situation.

Animals↗
PubMed1989

Plasmin and plasminogen in bovine milk: a relationship with involution?

A total of 774 individual milk samples were collected from 66 Holstein cows between October 1987 and April 1988. Samples were analyzed for plasmin, plasminogen, and SCC. An increase in SCC from less than 250,000/ml to more than 1,000,000/ml resulted in an increase of plasmin, plasminogen, and serum albumin by 105, 74, and 140%, respectively. Plasminogen, plasmin, and serum albumin followed similar trends that are expected for components from blood that gain access to the alveolar lumen through ruptured epithelium caused by mastitis. Increased plasmin is the direct result of this process rather than an increase in activation of plasminogen to plasmin. The plasminogen to plasmin ratio supports this interpretation, being 4.7 at 250,000 SCC/ml and 4.0 when SCC exceeded 1 million/ml. Plasmin and plasminogen concentrations were also increased during lactation to reach peak values immediately before the dry period. However, in this case, ratio of plasminogen to plasmin was 6.55 during early lactation and decreased by half to 3.29 during the latest stage, indicating that considerable activation of plasminogen to plasmin occurred during the latter part of lactation. Mammary epithelium is not compromised at this stage, as shown by low (.8 mg/ml) serum albumin concentration in milk. Two mechanisms responsible for increased milk plasmin include influx of plasmin from blood during mastitis and increased activation of plasminogen as lactation progresses.

Animals↗
PubMed1992

Distribution of plasminogen and plasmin in fractions of bovine milk.

The relative amounts of immunoreactive plasminogen and active plasmin in different fractions of bovine milk were examined. Raw milk was centrifuged to separate skim, cream, and a somatic cell pellet. Skim milk was centrifuged to separate milk serum and casein micelles. Milk fat globule membranes were isolated from the cream fraction of bovine milk. Proteins from somatic cells were isolated following sonication of the cells. Western blot analysis showed the presence of several forms of plasminogen in bovine milk. The predominant forms of plasminogen identified following electrophoresis under nonreducing conditions were proteins with approximate molecular weights of 88,000, 152,000, and 160,000. The predominant forms of plasminogen identified after electrophoresis under reducing conditions were two proteins with approximate molecular weights of 88,000 and 50,000. The highest amount (82% of the total plasminogen), as determined by an ELISA, was associated with the casein fraction. Lower plasminogen concentrations were associated with the serum, cream fractions, and milk fat globule membranes. The SDS-PAGE of the cream and milk fat globule membranes indicated that some casein was present in both fractions. Thus, the low plasminogen concentrations in these fractions may be associated with the caseins there. No immunoreactive plasminogen was present in the somatic cells. Active plasmin was present in the same milk fractions in which plasminogen was detected: casein, serum, and cream.

Animals↗