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PubMed1987

Stimulation of plasminogen activator production by dimethyl sulfoxide in Chinese hamster ovary cells.

The production of plasminogen activator activity in an auxotrophic mutant of the Chinese hamster ovary cell line was found be greatly stimulated by low concentrations of dimethyl sulfoxide. The production of both cell-associated and excreted plasminogen activator activities was stimulated maximally by dimethyl sulfoxide at a concentration of 2.5%. The stimulation of plasminogen activator activity production was found to be completely inhibited by actinomycin D and cycloheximide but not by mitomycin C, implying that new protein and RNA syntheses were required for this process. Using specific antibodies against plasminogen activator, the presence of a tissue-type plasminogen activator could only be detected in dimethyl sulfoxide treated cells. The dimethyl sulfoxide induced plasminogen activator production was observed only in a mutant auxotrophic for adenosine, glycine, and thymidine but not in wild-type cells. The ability of dimethyl sulfoxide to induce the synthesis of plasminogen activator was lost when the cells were hybridized with another complementary auxotrophic mutant. This implies that the ability of dimethyl sulfoxide to stimulate the production of plasminogen activator may be related to the auxotrophic mutation in this cell.

Animals↗
PubMed2006

Differential binding of plasminogen, plasmin, and angiostatin4.5 to cell surface beta-actin: implications for cancer-mediated angiogenesis.

Angiostatin4.5 (AS4.5) is the product of plasmin autoproteolysis and consists of kringles 1 to 4 and approximately 85% of kringle 5. In culture, cancer cell surface globular beta-actin mediates plasmin autoproteolysis to AS4.5. We now show that plasminogen binds to prostate cancer cells and that the binding colocalizes with surface beta-actin, but AS4.5 does not bind to the cell surface. Plasminogen and plasmin bind to immobilized beta-actin similarly, with a Kd of approximately 140 nmol/L. The binding is inhibited by epsilon-aminocaproic acid (epsilonACA), indicating the requirement for a lysine-kringle domain interaction. Using a series of peptides derived from beta-actin in competitive binding studies, we show that the domain necessary for plasminogen binding is within amino acids 55 to 69 (GDEAQSKRGILTLKY). Substitution of Lys61 or Lys68 with arginine results in the loss of the ability of the peptide to block plasminogen binding, indicating that Lys61 and Lys68 are essential for plasminogen binding. Other actin peptides, including peptides with lysine, did not inhibit the plasminogen-actin interaction. AS4.5 did not bind actin at concentrations up to 40 micromol/L. Plasminogen, plasmin, and AS4.5 all contain kringles 1 to 4; however, kringle 5 is truncated in AS4.5. Isolated kringle 5 binds to actin, suggesting intact kringle 5 is necessary for plasminogen and plasmin to bind to cell surface beta-actin, and the truncated kringle 5 in AS4.5 results in its release from beta-actin. These data may explain the mechanism by which AS4.5 is formed locally on cancer cell surfaces and yet acts on distant sites.

Actins↗
PubMed2005

The nine residue plasminogen-binding motif of the pneumococcal enolase is the major cofactor of plasmin-mediated degradation of extracellular matrix, dissolution of fibrin and transmigration.

The glycolytic enzyme alpha-enolase represents one of the nonclassical cell surface plasminogen-binding proteins of Streptococcus pneumoniae. In this study we investigated the impact of an internal plasminogen-binding motif of enolase on degradation of extracellular matrix and pneumococcal transmigration. In the presence of host-derived plasminogen activators (PA) tissue-type PA or urokinase PA and plasminogen S. pneumoniae expressing wild-type enolase efficiently degraded Matrigel or extracellular matrix (ECM). In contrast, amino acid substitutions in the nine residue plasminogen-binding motif of enolase significantly reduced degradation of ECM or Matrigel by mutated pneumococci. Similarly, recombinant wild-type enolase but not a mutated enolase derivative that lacks plasminogen-binding activity efficiently degraded ECM and Matrigel, respectively. In particular, bacterial cell enolase-bound plasmin potentiated dissolution of fibrin or laminin and transmigration of pneumococci through a fibrin matrix. In conclusion, these results provide evidence that the enolase is the major plasminogen-binding protein of pneumococci and that the nine residue plasminogen-binding motif of enolase is the key cofactor for plasmin-mediated pneumococcal degradation and transmigration through host ECM.

Amino Acid Motifs↗
PubMed1995

Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice.

BACKGROUND: Circumstantial evidence suggests that the plasminogen/plasmin system plays a role in many biological processes, including hemostasis, cell migration, and development. METHODS AND RESULTS: The in vivo function of the plasminogen/plasmin system was studied by generation of plasminogen-deficient (Plg-/-) mice. Inactivation of the murine plasminogen-gene (Plg) was achieved by replacing, via homologous recombination in embryonic stem cells, genomic sequences encoding the exons containing the catalytic site amino acids His605 and Asp648 with a neomycin phosphotransferase expression cassette. Germline transmission of the mutated allele, as determined by Southern blot hybridization and polymerase chain reaction, was obtained via blastocyst injection. Mendelian inheritance of the inactivated plasminogen allele was observed, and homozygous-deficient mice (Plg-/-) displayed normal viability but retarded growth up to at least 12 weeks of age. At 8 weeks of age, body weight was 21.8 +/- 1.2 g (n = 10) for wild-type (Plg+/+) mice, 21.0 +/- 1.1 g (n = 16) for heterozygous-deficient (Plg+/-) mice, and 17.4 +/- 1.3 g (n = 12) for Plg-/- mice; P < .05 versus Plg+/+ or Plg+/-. None of 36 Plg+/+ or 65 Plg+/- mice but 7 of 37 Plg-/- mice (19%) developed rectal prolapse at 7.4 +/- 0.6 weeks of age (P = .03 versus Plg+/+ and P = .003 versus Plg+/-); 4 of 37 Plg-/- mice (11%) became runted and apathic at 5.3 +/- 0.3 weeks of age (P = .041 versus Plg+/-); and 6 of 37 Plg-/- mice (16%) died prematurely at 8.8 +/- 1.7 weeks of age (P = .057 versus Plg+/+ and P = .029 versus Plg+/-). Although male and female Plg-/- mice were able to sire offspring, the fertility of Plg-/- female mice was reduced, possibly owing to their impaired health. Levels of plasminogen-related antigen in plasma, measured by ELISA, were 84 +/- 8 micrograms/mL (n = 4) in Plg+/+, 35 +/- 2 micrograms/mL (n = 3) in Plg+/-, and 0.076 +/- 0.032 microgram/mL (n = 6) in Plg-/- mice (P < .001 versus Plg+/- and Plg+/+). Plasmin activity generated by urokinase activation was unmeasurable in Plg-/- mice (< 5% of Plg+/+ mice). Plasminogen-specific immunoreactivity was observed in hepatocytes from Plg+/+ mice but not from Plg-/- mice (< 10% of Plg+/+ mice). Neither native nor variant plasminogen mRNA nor translation products could be identified by Northern or Western blot of liver extracts from Plg-/- mice. Spontaneous lysis within 24 hours of a 125I-fibrin-labeled pulmonary plasma clot was 85 +/- 5% (n = 5) in Plg+/+ mice, 62 +/- 7% (n = 3) in Plg+/- mice, and -2 +/- 1% (n = 3) in Plg-/- mice (P < .001 versus Plg+/- and Plg+/+). Delayed clot lysis within 72 hours was 33 +/- 1% (n = 3) in tPA-/- mice and 26 +/- 2% (n = 3) in Plg-/- mice (P = .054). Histological examination of several organs revealed fibrin deposition in the liver; lung; and in the stomach, associated with gastric ulcers, in 6- to 12-week-old Plg-/- mice but not in Plg+/+ or Plg+/- littermates. CONCLUSIONS: Plasminogen-deficient mice survive embryonic development but develop spontaneous fibrin deposition due to impaired thrombolysis and suffer retarded growth and reduced fertility and survival. The Plg-/- phenotype is reminiscent of the combined tPA-/-:uPA-/- phenotype, which suggests that there is no significant additional pathway for physiological plasminogen activation in mice.

Animals↗
PubMed1991

Stroke in a young adult with familial plasminogen disorder.

BACKGROUND: We report a new plasminogen disorder detected in a 29-year-old man with a cerebellar infarct. To our knowledge, plasminogen disorders have not been previously linked with stroke. SUMMARY OF REPORT: Tests for well-recognized causes of stroke were negative. However, a screening hypercoagulation profile indicated low functional levels of plasminogen activity. Immunologic plasminogen (Laurell technique) was 64% of normal (normal level, 80-130%). The rate of plasmin generation induced by adding urokinase to plasma was also low. Plasminogen activator, free protease, and alpha 2-plasmin inhibitor levels were normal. Family studies detected a similar plasminogen abnormality in the patient's mother and 9-year-old son, both of whom are asymptomatic. CONCLUSIONS: Our patient shows a congenital, heterozygous, functionally abnormal plasminogen. Although the exact relationship to stroke is unclear, we suggest screening young patients with unexplained stroke for plasminogen defects using commercially available assay systems.

Adult↗
PubMed1984

Alveolar macrophage plasminogen activator.

Plasminogen activator is a neutral serine protease secreted by many different cells, including activated peritoneal macrophages, which can mediate both inflammation and fibrinolysis and perhaps cytolysis of tumor cells. Secretion of plasminogen activator by rabbit alveolar macrophages derived from normal animals and rabbits pretreated with bacillus Calmette-Guérin (BCG) to activate these macrophages was examined. Plasminogen activator was secreted into media of cultured alveolar macrophages, but was not present within the cells. Secretion, which was dependent upon the presence of viable cells, could be blocked by protein synthesis inhibitors and enhanced by concanavalin A and phorbol myristate acetate. The inhibition profile of rabbit alveolar macrophage plasminogen activator is consistent with that of a serine protease. Plasminogen activator is present in two forms with molecular weights of 28,000 and 45,000. Alveolar macrophage plasminogen activator was secreted in cultures from most rabbits (17 of 23) pretreated with BCG, but rarely in those from normal animals (2 of 14). Lavage fluids from many rabbits contained viable Bordetella bronchiseptica, but the presence of this organism showed no correlation with secretion of plasminogen activator. Rabbit alveolar macrophages secrete a plasminogen activator similar to that secreted by mouse peritoneal macrophages as described previously. Secretion is enhanced by activation of alveolar macrophage populations.

Animals↗
PubMed1983

Macrophage cell lines behave as activated macrophages in the production and regulation of plasminogen activator.

Seven macrophagelike cell lines, WEHI-3, J774, RAW264, FC-1, P388D-1, PU5-R, and PU5-1.8, commonly used as in vitro models of macrophage function, were studied for their fibrinolytic activity in the presence and absence of purified plasminogen. All cell lines, as well as the freshly harvested peritoneal macrophages, produced plasminogen activator, as indicated by the levels of fibrinolytic activity in the presence of plasminogen. However, fibrinolytic proteolysis was most efficiently measured by direct attachment to 125I-fibrin plates, a method which measures both secreted and cell-membrane-associated plasminogen activator. Other non-plasminogen-dependent fibrinolytic activities were also produced by all cells studied and secreted by WEHI-3, FC-1, RAW-264, and thioglycollate-elicited macrophages. Activation of the thioglycollate-elicited macrophages with macrophage activation factor (MAF) induced threefold higher levels of plasminogen activator production but MAF treatment had no effect on the level of activity produced by macrophagelike cell lines. Indeed, the macrophagelike cell lines produced plasminogen activator at levels seen with MAF-activated thioglycollate-elicited macrophages. We conclude that these cell lines constitutively produce activators of plasminogen and, in their failure to respond to MAF, behave as activated macrophages.

Animals↗
PubMed1990

Stimulation of radiation-impaired plasminogen activator release by phorbol ester in aortic endothelial cells.

Ionizing radiation has been reported to affect the fibrinolytic activity of exposed tissue. With cultured bovine aortic endothelial cells, radiation suppresses the release of plasminogen activator to the conditioned media, with a concomitant increase in intracellular plasminogen activator. Thus study was undertaken to determine whether radiation-impaired plasminogen activator release can be modified by phorbol ester. We exposed cultured bovine aortic endothelial cells to a sterilizing dose of 10 Gy of gamma-rays and found the treatment led to cell injury, as evidenced by an increased release of prelabeled chromium, and to a reduction of plasminogen activator in the conditioned media with elevated intracellular plasminogen activator in irradiated cells. Phorbol ester enhanced plasminogen activator activity in both sham-irradiated and irradiated endothelial cells. It was interesting to note that the increased plasminogen activator in phorbol ester-stimulated sham-irradiated cells was largely retained inside the cell, while it was released to the conditioned media in irradiated cells. Apparently, altered plasminogen activator activity of radiation-sterilized endothelial cells can be modified by exogenous stimuli.

Animals↗
PubMed1999

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

Adolescent↗
PubMedDate not supplied

Plasma plasminogen activator inhibitor-1 activity in normoglycemic hypertriglyceridemic north Asian Indian subjects: a preliminary case-control study.

BACKGROUND: Recent evidence suggests that increased activity of plasma plasminogen activator inhibitor-1, an important component of the insulin resistance syndrome, plays a crucial role in the pathogenesis of atherosclerosis. METHODS AND RESULTS: In this case-control study, relationships between plasma plasminogen activator inhibitor-1 activity, serum triglyceride levels and hyperinsulinemia were explored in 40 non-diabetic patients with primary hypertriglyceridemia (Group 1) and 40 non-diabetic normotriglyceridemic controls (Group 2) matched for potential confounders like smoking and physical activity. Mean values of fasting serum insulin levels were increased in Group 1 (p>0.05). Hyperinsulinemia was observed in 14 (17.5%) individuals in Group 1 and 11 (13.8%) individuals in Group 2. Mean plasma plasminogen activator inhibitor-I activity in Group 1 (9.8+/-8.4 IU) was higher than in Group 2 (7.0+/-7.7 IU), though the difference was not significant (p>0.05). However, when only subjects with elevated levels of plasma plasminogen activator inhibitor-1 activity were taken into account, mean values were significantly higher in Group 1 (p<0.05). The plasma plasminogen activator inhibitor-1 activity was higher in subjects with body mass index >25 in both the groups, significantly so in males (p=0.05). Hyperinsulinemic subjects with a body mass index >25 and raised serum triglyceride levels had higher mean values of plasma plasminogen activator inhibitor-1 activity (18.42+/-11.15 IU) than subjects with similar characteristics and normal triglyceride levels (14.22+/-8.20 IU, p<0.05). CONCLUSIONS: Though in the current study a trend for hyperinsulinemia and high plasma plasminogen activator inhibitor-1 activity was observed in hypertriglyceridemic subjects, a larger study is needed to achieve significant differences and correlations. Obese male subjects, irrespective of their lipid profile, are at risk for thrombotic events in view of their significantly higher plasma plasminogen activator inhibitor-1 values. Procoagulant tendency is further enhanced if hypertriglyceridemia and hyperinsulinemia are added on to obesity.

Adolescent↗
PubMed1992

[Features of the interaction of Glu- and Lys-forms of plasminogen with native and partially hydrolyzed fibrin].

Glu- and Lys-plasminogen interaction with native and desAABB-fibrin obtained from fibrinogen partially hydrolyzed by plasmin was studied. It was found that native fibrin adsorbs 6 times more Lys-plasminogen as compared to the native form of the proenzyme. The range of the Lys-plasminogen binding does not change, if part of the fibrinogen molecules hydrolyze down to X-fragments. At the same time, the appearance in the system of 1% Xi-fragments leads to a 6-fold increase in the Glu-plasminogen binding. The amount of adsorbed Glu-plasminogen reaches the level of Lys-plasminogen adsorption both in the native and partially hydrolyzed fibrin. It was found that kringle K 1-3 or 6-aminohexanoic acid at saturating for high-affinity lysine-binding sites concentrations do not influence the Glu-plasminogen binding to native fibrin but inhibit it when the partially purified form is used. It is assumed that the manyfold increase of the Glu-plasminogen binding to partially hydrolyzed fibrin is due to the alteration of the proenzyme conformation at the initial steps of fibrin hydrolysis during the formation of Xi fragments.

Aminocaproic Acid↗
PubMed2004

Genetic analysis of Streptococcus uberis plasminogen activators.

BACKGROUND & OBJECTIVES: Streptococci produce a diverse range of secreted plasminogen activators capable of converting mammalian plasminogen to plasmin in a species-specific manner. In all examples to date, the host animal's plasminogen and that of a number of additional species have been shown to interact with these molecules leading to the conclusion that the pathogenesis of streptococci is in some way dependent upon activation of host plasminogen. PauA was the first plasminogen activator described from Streptococcus uberis, a pathogen frequently isolated from cases of bovine mastitis. Recently, a second S. uberis plasminogen activator (PauB) was identified from a Danish mastitis isolate. Interestingly, the pauB open reading frame occupied the locus normally filled by pauA. In the present study a genetic screen of streptococcal and field isolates frequently associated with mastitis was undertaken to assess the distribution, chromosomal location and sequence variation of these putative virulence factors. METHODS: Southern analysis of a diverse panel of streptococci and additional bacterial isolates frequently associated with bovine mastitis was performed using pauA and pauB probes. Sequence variation of PauA was assessed at the protein level following nucleotide sequence analysis of pauA alleles amplified from isolates picked from different geographical locations. RESULTS: We observed plasminogen activators to be universally distributed amongst S. uberis. A pauA allele was identified in all but one strain of S. uberis. This strain had a pauB allele substituted for pauA at the same locus. The remarkably low level of sequence variation demonstrated by PauA was further restricted to a limited number of residues within the molecule. INTERPRETATION & CONCLUSION: The high prevalence of PauA alleles in field isolates of S.uberis supported the observation that plasminogen activators are likely to confer an advantage with respect to colonization and growth. The findings of the present study support the theory that PauA plays a critical role in the pathogenesis of S. uberis.

Base Sequence↗
PubMed1990

[Mechanisms of activation of tissue-type plasminogen activator].

Tissue-type plasminogen activator (t-PA) is an important component of the fibrinolytic system. t-PA is released into the circulation as a one-chain peptide with little enzyme activity. There exist several mechanisms which enhance plasminogen activation rate by t-PA: 1. activation of enzyme activity of one-chain t-PA by fibrin binding; 2. activation of enzyme activity by transforming one-chain to two-chain t-PA by plasmin; 3. stimulation of plasminogen activation by forming a ternary complex of t-PA, plasminogen and fibrin; 4. stimulation of plasminogen activation by forming Lys-plasminogen, which has a higher affinity to fibrin and is a better substrate for t-PA than Glu-plasminogen; 5. enhancement of ternary complex concentration after initiation of fibrinolysis due to tighter binding of t-PA and plasminogen to partially degraded fibrin.

Animals↗
PubMed1983

Production of plasminogen activator in a melanoma cell line.

A melanoma cell line (Bowes) was found to produce plasminogen activator even on its growing phase, and the rate of plasminogen activator production was rather constant. The production of plasminogen activator was proportional to the cell number. Morphologically, no specific features for plasminogen activator production were seen. Plasminogen activator was observed in the lysate of this cell line only when the cell number was large. The extracellular plasminogen activator activity was higher than the intracellular plasminogen activator activity, suggesting the existence of a secretion mechanism for the plasminogen activator.

Cell Count↗
PubMed1983

Role of plasminogen in matrix breakdown by neoplastic cells.

Destruction of the extracellular matrix is often observed during tumor invasion, and proteolytic enzymes may participate actively in the degradation of matrix proteins. The present report elucidates the role of plasminogen in the degradation by tumor cells of an in vitro elaborated extracellular matrix. Matrices produced by rat smooth muscle cells in the presence of [3H]proline or [3H]fucose were used as substrates for human fibrosarcoma cells (HT-1080), mouse melanoma cells (B16F1), or human rhabdomyosarcoma cells (RD). All three cell lines degraded part of the glycoprotein compartment of the matrix. HT-1080 cells digested the matrices in a density-dependent manner, and while matrix glycoprotein degradation was plasminogen-dependent at the beginning of the experiment and at low cell densities, the zymogen was not essential for further glycoprotein digestion at high cell densities. Depletion of plasminogen from the growth medium resulted in a threefold reduction of matrix degradation by B16F1 cells showing a distinct plasminogen dependency at low cell numbers. RD cells digested only matrix glycoproteins, and this degradation was completely dependent on the presence of plasminogen at all cell densities. These results suggested that plasmin generated from plasminogen by a tumor cell-associated plasminogen activator may be most important for matrix hydrolysis at low cell densities, and while certain tumor cell lines showed a definite plasminogen-independent matrix degradation with increased cell numbers, other neoplastic cells hydrolyzed the matrix only in the presence of the zymogen at all cell densities.

Animals↗
PubMed1983

Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay.

A two-site immunoradiometric assay for human extrinsic (tissue-type) plasminogen activator was developed by using rabbit antibodies raised against plasminogen activator purified from human melanoma cell culture fluid. Samples of 100 microliters containing 1 to 100 ng/ml plasminogen activator were incubated in the wells of polyvinyl chloride microtiter plates coated with antibody. The amount of bound extrinsic plasminogen activator was quantitated by the subsequent binding of 125I-labeled affinospecific antibody. The mean level of plasma samples taken at rest was 6.6 +/- 2.9 ng/ml (n = 54). This level increased approximately threefold by exhaustive physical exercise, venous occlusion, or infusion of DDAVP. Extrinsic plasminogen activator in plasma is composed of a fibrin-adsorbable and active component (1.9 +/- 1.1 ng/ml, n = 54, in resting conditions) and an inactive component that does not bind to a fibrin clot (probably extrinsic plasminogen activator-proteinase inhibitor complexes). The fibrin-adsorbable fraction increased approximately fivefold to eightfold after physical exercise, venous occlusion, or DDAVP injections. Potential applications of the immunoradiometric assay are illustrated by the measurement of extrinsic plasminogen activator in different tissue extracts, body fluids, and cell culture fluids and in oocyte translation products after injection with mRNA for plasminogen activator.

Culture Techniques↗
PubMed1981

Binding of 99mTc plasminogen on fibrin.

Binding of plasminogen to fibrin was studied in vitro and in vivo using 99mTc Glu- and Lys-plasminogen. Binding of Glu-plasminogen on the clot was not observed in vitro, and in vivo in the dog. Conversely, the binding of Lys-plasminogen to fibrin displays a linear relationship to the concentration of Lys-plasminogen, up to doses exceeding equimolarity; thus suggesting the existence of several Lys-plasminogen binding sites on fibrin. Binding levels were identical, regardless of whether plasminogen was incubated in normal plasma or in plasma devoid of antiplasmin. In the dog, Lys-plasminogen bound specifically to the clot, however, clot sites could not be localized by scintigraphy in the dog or in man.

Animals↗
PubMed1981

Activated factor B (Bb) of the alternative pathway of complement activation cleaves and activates plasminogen.

Activated Factor B (Bb), the central serine esterase of the alternative pathway of complement activation, exhibits restricted substrate specificity in the complement system for C3 and C5. The results presented here indicate that Bb can cleave and activate plasminogen in an experimental system containing purified plasminogen and Bb; complement cellular intermediate bearing the Bb-enzyme; or cobra venom factor-stabilized Bb-enzyme (CVF,Bb). Cleavage of plasminogen by Factor Bb generated 2 disulfide-linked polypeptides with apparent m.w. of 64,000 and 25,000 to 32,000 (SDS-PAGE). Complement cellular intermediates containing the C3b, Bb-enzyme cleave 40 to 80% of 4.5 micrograms of 125I-labeled plasminogen during 30 min of incubation at 37 degrees C; native Factor B was inactive; and anti-Factor Blg inhibited by 100% the plasminogen cleavage mediated by complement cellular intermediates bearing the Bb-enzyme. Fibrinolytic activity was detected in plasminogen activator (PA) assays when purified plasminogen and 125I-labeled fibrin tubes were incubated with Bb, CVF, Bb, or complement cellular intermediates bearing the C3b,Bb-enzyme: 10 micrograms Bb released 40 to 65% of the 125I-fibrin released by 5 micrograms urokinase in 4 hr at 37 degrees C. Plasminogen activator activity of the C3b,Bb-enzyme was found to be regulated in serum. At dilutions of NHS 1:50, the PA-activity of 1.6 micrograms Bb was 100% inhibited, and at a 1:250 dilution, 50% inhibition was observed. This report describes a novel activity for the Bb-enzyme, which constitutes the C3/C5-convertase of the alternative pathway of complement activation.

Complement Activation↗