Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLASMINOGEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed2003

Tissue-type plasminogen activator and its inhibitor plasminogen activator inhibitor type 1 are coordinately expressed during ovulation in the rhesus monkey.

Ovulation is a gonadotropin-controlled process that is essential for the propagation of all mammalian species. In the present study, we used a pregnant mare serum gonodotropin/human chorionic gonadotropin (hCG)-induced, synchronized ovulation model in rhesus monkeys and systematically investigated the roles of the plasminogen activator (PA) system in the ovulatory process of the primate. At different follicular developmental stages throughout the periovulatory period, samples of ovaries, granulosa cells, and theca-interstitial cells as well as follicular fluid were collected, and levels of PA and PA inhibitor type-1 (PAI-1) were evaluated by fibrin overlay, reverse fibrin overlay, Northern blot analysis, and in situ hybridization, respectively. We showed that in response to an injection of ovulation-triggering hCG, which mimics the preovulatory surge of LH in the circulation, granulosa cell-derived tissue-type PA (tPA) was substantially elevated in preovulatory follicles and reached its maximum level just before ovulation. Although theca-interstitial cell-derived PAI-1 was also stimulated by pregnant mare serum gonodotropin and hCG treatments, however, the maximum level of PAI-1 appeared 12 h earlier than that of tPA. When ovulation approached, accompanying the highest tPA level in the preovulatory follicles, the follicular PAI-1 level declined dramatically to its minimum value. Moreover, our data on the expression of follicular PA and PAI-1 over the periovulatory period were reinforced by results obtained at the mRNA level. Our data suggest that the coordinated expression of tPA and PAI-1 may be of importance for the follicular rupture process during ovulation in the primate.

Aging↗
PubMed1995

Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1.

Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers, and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10(-7) mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10(-8) mol/L E2 plus 10(-7) mol/L MPA virtually eliminated both tPA activity (99% inhibition; P < 0.005) and uPA activity (93% inhibition; P < 0.005); the reductions in levels of the corresponding antigens were only about 50% of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P < 0.05) and uPA (P < 0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation.

Cells, Cultured↗
PubMed1992

[Plasminogen activators and plasminogen activator inhibitor type-1 in human endometrium].

Two types of plasminogen activator (PAs) are present in human endometrium, and their contents vary with the different phases of menstrual cycle, i.e. high in the proliferative phase and low in the secretory phase. In the present study by immunohistochemical technique, both uPA and tPA antigens were demonstrated in the stromal and glandular cells of the endometrium. In cell culture, tPA was released only from stromal cells and uPA only from glandular cells as determined by SDS-PAGE followed by fibrin overlay technique, but PA inhibitor type-1 (PAI-1) was secreted by both stromal and glandular cells. Furthermore, secretion of PAs from endometrial cells was enhanced by adding estradiol and markedly inhibited by progesterone in a dose dependent manner, while the PAI reacted just in the opposite way. The effect of the peptide hormones, hCG, GnRH, PRL, as well as cAMP in cell culture on the secretion of PAs and PAI was similar to that of estradiol, while forskolin demonstrated definitely more stimulative effect on tPA than uPA. Taking into account of the finding of the present study, it appears that, under hormonal control, a balance between PAs and PAI in the endometrium exists. The physiological roles of the PAs and PAI in the endometrium were discussed.

Adult↗
PubMed1990

Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo.

The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells.

Animals↗
PubMedDate not supplied

Effect of transforming growth factor-beta 1 on plasminogen activators and plasminogen activator inhibitor-1 in renal glomerular cells.

Recent evidence suggests that the balance between serine proteases and their inhibitors is central to the maintenance of the glomerular extracellular matrix. We have characterised the urokinase type and the tissue type plasminogen activators (PA) and their inhibitor, PAI-1, secreted from glomerular epithelial and mesangial cells as well as their co-cultures and have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) on the production of such species. Similar data were derived from whole glomeruli suspensions. TGF-beta 1 increased PAI-1 production significantly in epithelial and mesangial cells as well as in whole glomeruli, while PA production was decreased; platelet-derived growth factor had no effect. These effects are consistent with a possible decrease in matrix proteolysis, suggesting a mechanism by which TGF-beta 1 may enhance mesangial matrix accumulation, a characteristic of many forms of glomerular disease.

Epithelial Cells↗
PubMed1990

Plasminogen activators and their inhibitors in the neuromuscular system: I. Developmental regulation of plasminogen activator isoforms during in vitro myogenesis in two cell lines.

Plasminogen activators (PAs), were estimated qualitatively and quantitatively in two different clonal murine skeletal muscle cell lines. Both cell lines produced the two major types of PAs found in mammalian cells, urokinase-type (uPA) and tissue type (tPA). These two lines are models for the study of myogenesis in vitro, but differ in several growth and differentiation characteristics. Because of their possible involvement in these characteristics we assayed the expression of PAs in both cell systems during development in culture. Utilizing fibrin zymography two isoforms of tPA were detected. One co-migrated with human tPA at 75 kd and another may represent a tPA:inhibitor complex at 105 Kd. Several isoenzymes of uPA were detected and these changed depending on whether cell homogenates or conditioned medium was analyzed and whether myogenic cells were at single-cell myoblast or multi-nucleated myotube stage. Species-specific antisera to mouse uPA identified 4 uPA bands in muscle cell medium and 5 in cell layers. Antigenic uPA bands also varied depending on stage of myogenesis. Quantitative amidolytic studies using chromogenic substrates showed that maximal PA activity, both uPA and tPA, occurred at the time of myoblast fusion. Furthermore, uPA activity in membranes increased during myogenesis, while both uPA and tPA in medium decreased after fusion. These studies indicate that muscle PA expression is developmentally regulated and may correlate with growth and differentiation in skeletal muscle.

Animals↗
PubMed2001

Selective behaviors altered in plasminogen-deficient mice are reconstituted with intracerebroventricular injection of plasminogen.

In vitro studies demonstrate a role for the plasminogen (Plg) system in neurological function and recently in vivo studies show a role of the Plg system in neurodegeneration after the injection of an excitotoxic agent. Differences in the development of neurological function, however, have not been demonstrated in the Plg-deficient (Plg-/-) mice compared to wild-type (WT) mice. The role of Plg system in neurological function may relate to remodeling which occurs in response to various environmental challenges. In this study, behaviors (open field, grooming, hind-leg gait, water maze, and acoustic startle reflex) were tested in the Plg-deficient and WT mice at 6-8 weeks of age. Grooming, a response to the stress of an open field or fur moistening, was increased in the Plg-/--deficient mice compared to WT mice, and the acoustic startle reflex (ASR) was markedly decreased in the Plg-/- mice. The reduced ASR in Plg-/- mice occurred in mice with a mixed C57BL:129 background or in mice with a C57BL background. Plg was required for the ASR, since a deficiency of the Plg activators, urokinase (uPA) or tissue Plg activator (tPA), did not cause a reduction in the ASR compared to their WT control. Infusion of Plg directly into the brain was effective in restoring the ASR in the Plg-/- mice, but had no effect on the ASR of WT mice. Peripheral bolus injections of Plg or infusion into the jugular vein were ineffective in restoring the ASR in the Plg-/- mice. These results indicate that Plg is required for the appropriate response to the environmental challenge of a sudden loud sound, and that the response can be restored in Plg-/- mice by directly infusing Plg into the brain.

Animals↗
PubMed1997

Introduction of an RRHR motif into chicken urokinase-type plasminogen activator (ch-uPA) confers sensitivity to plasminogen activator inhibitor (PAI)-1 and PAI-2 and allows ch-uPA-mediated extracellular matrix degradation to be controlled by PAI-1.

Comparison of the amino acid sequence of the chicken and human urokinase-type plasminogen activators (uPAs) revealed that the putative PAI-binding site found in the variable region 1 (VR1) loop of mammalian PAs is absent in the homologous region of ch-uPA. ch-uPA, unlike mammalian PAs, also appears to be refractory to inhibition by human PAIs and as a naturally occurring PAI-resistant variant, constitutes a unique model system for assessing the functional relevance of the PAI-binding site. Therefore, we molecularly constructed a ch-uPA, ch-uPA(RRHR), which contains the putative PAI-binding motif RRHR (residues 192-195) in its VR1 loop. As a result of this substitution, the second-order rate constant of inhibition of PAI-1 increased approximately 700-fold from 4.50 x 10(4) M(-1) x s(-1) for wild-type ch-uPA to 3.02 x 10(7) M(-1) x s(-1) for ch-uPA(RRHR), and the ability to form SDS-stable, uPA-PAI-1 complexes increased approximately 1000-fold. Furthermore, the interaction of ch-uPA(RRHR) with PAI-2 was also substantially enhanced, while the interaction with other members of the serine proteinase inhibitor superfamily, protein nexin 1, alpha1-PI, and C1-inhibitor, was unaffected indicating that the RRHR motif is not a general serine proteinase inhibitor binding site. Finally, we show that extracellular matrix degradation by cells expressing ch-uPA(RRHR) is inhibited by PAI-1 in a dose-dependent manner, while matrix breakdown by cells expressing wild-type ch-uPA is unaffected by PAI-1. Thus acquisition of sensitivity to PAI-1 through a structural motif that enhances the specificity of the protease-inhibitor interaction confers to ch-uPA an added level of regulation in the context of the degradative cellular phenotype.

Amino Acid Sequence↗
PubMed1989

Enhanced plasminogen activator production of Syrian hamster embryo cells transformed by chemicals or the c-Ha-ras oncogene: type of plasminogen activators involved and their contribution to the transformed phenotype.

The plasminogen activator (PA) activity produced by Syrian hamster embryo (SHE) cells in different stages of neoplastic conversion was analysed. PA activity was characterized immunologically and by SDS-PAGE. Normal SHE cells had a very low PA activity. Although activity of either the tissue type of PA (t-PA) or the urokinase type (u-PA) or both were found to be increased in most immortal or transformed SHE cells, there was no correlation between enhanced production of a particular PA type and the development of the immortal or transformed phenotype. However, within a group of cell lines clonally derived from a culture of immortal cells, a positive correlation was found between extracellular t-PA, but not u-PA, activity and cellular growth rate. For the Syrian hamster PA species, crossreacting with anti-human u-PA, a mol. wt of 39 kd was observed. For the Syrian hamster PA species, crossreacting with anti-human t-PA, multiple species were found with mol. wts of 98, 72 and 59 kd respectively. Evidence was obtained that the 72-kd species represents the intact enzyme, the 59-kd species a partial digestion product thereof and the 98 kd species, which often appears as a doublet, a complex of either of these species with an inhibitor, likely to be secreted by the same cells. Finally, our data suggest a novel mechanism for the enhancement of t-PA activity of transformed cells, namely by a decrease in the effective extracellular amount of putative inhibitor.

Animals↗
PubMed2002

The ratio of plasminogen activator inhibitor type-1 activity to the concentration of plasminogen activator inhibitor type-1 protein in diabetes: adding insult to injury.

BACKGROUND: This study was performed to delineate the relationship between plasminogen activator inhibitor type-1 (PAI-1) activity and PAI-1 protein to characterize the functional importance of elevated PAI-1 in diabetes. METHODS: PAI-1 activity (chromogenic substrate kinetic assay) and protein (enzyme-linked immunosorbent assay) were assayed in baseline central venous catheter-acquired samples from 170 patients with type 2 diabetes studied in the Troglitazone Atherosclerosis Regression Trial (TART). RESULTS: The data demonstrated that the ratio of PAI-1 activity to the concentration of PAI-1 protein is increased as a function of increasing concentrations of PAI-1 protein in blood. CONCLUSIONS: The results demonstrate that the ratio of PAI-1 activity to the concentration of PAI-1 protein is higher when the concentration of PAI-1 is elevated. The nonlinearity appears to depend on the fact that the rate of disappearance of PAI-1 activity in blood is a function of the concentration of PAI-1 protein.

Diabetes Mellitus, Type 2↗
PubMed1989

Characterization of keratinocyte plasminogen activator inhibitors and demonstration of the prevention of pemphigus IgG-induced acantholysis by a purified plasminogen activator inhibitor.

To investigate the mechanisms by which cutaneous plasminogen activator (PA) may be regulated, we have tested cultured keratinocytes for the presence of PA inhibitors. Using biosynthetic labeling experiments with 35S-methionine in conjunction with specific antibody precipitation, we have shown that human keratinocytes in culture synthesized and secreted both PA inhibitor 1 and PA inhibitor 2. PA inhibitor 1 was present in conditioned media in the inactive form, but it could be detected with reverse phase autography. PA inhibitor 2 was detected by its ability to form complexes with 125I-uPA. Potential therapeutic relevance for cutaneous PA inhibitor 2 was suggested in skin organ culture experiments which demonstrated that purified PA inhibitor 2 from human placenta was able to prevent the acantholytic changes induced by pemphigus IgG.

Acantholysis↗
PubMed2004

Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness.

Mechanisms underlying airway hyperresponsiveness are not yet fully elucidated. One of the manifestations of airway inflammation is leakage of diverse plasma proteins into the airway lumen. They include fibrinogen and thrombin. Thrombin cleaves fibrinogen to form fibrin, a major component of thrombi. Fibrin inactivates surfactant. Surfactant on the airway surface maintains airway patency by lowering surface tension. In this study, immunohistochemically detected fibrin was seen along the luminal surface of distal airways in a patient who died of status asthmaticus and in mice with induced allergic airway inflammation. In addition, we observed altered airway fibrinolytic system protein balance consistent with promotion of fibrin deposition in mice with allergic airway inflammation. The airways of mice were exposed to aerosolized fibrinogen, thrombin, or to fibrinogen followed by thrombin. Only fibrinogen followed by thrombin resulted in airway hyperresponsiveness compared with controls. An aerosolized fibrinolytic agent, tissue-type plasminogen activator, significantly diminished airway hyperresponsiveness in mice with allergic airway inflammation. These results are consistent with the hypothesis that leakage of fibrinogen and thrombin and their accumulation on the airway surface can contribute to the pathogenesis of airway hyperresponsiveness.

Animals↗
PubMed1989

Plasminogen activator and plasminogen activator inhibitor in human preovulatory follicular fluid.

To evaluate the roles of plasminogen activator (PA) and PA inhibitor (PAI) in human ovulation, we obtained follicular fluid and granulosa cells from individual preovulatory follicles of patients undergoing gamete intrafallopian tube transfer. The follicular fluid samples (n = 25) were analyzed for total tissue-type PA antigen, PA enzyme activity by fibrin autography, PAI activity, PAI type 1 (PAI-1) antigen, and PAI-1 mRNA. The follicular fluid of preovulatory follicles contained low levels of total tissue-type PA antigen (less than 1 ng/mL). Fibrin autography experiments indicated little or no detectable PA activity associated with free or unbound PA. The results of the PAI activity assay and PAI-1 antigen determination support the concept of a relative abundance of PAI compared with PA. Hybridization analysis was used to measure the relative amounts of granulosa cell PAI-1 mRNA. The levels of PAI-1 mRNA correlate with follicular fluid PAI concentrations in individual follicles. Taken together, these results support the idea that there is very little free, or active, PA in follicular fluid of human preovulatory follicles, but there is an abundance of PAI. Furthermore, PAI-1 produced by the granulosa cells may represent a major form of PAI in follicular fluid.

Antigens↗
PubMed1987

Dexamethasone inhibition of tissue-type plasminogen activator (tPA) activity: paradoxical induction of both tPA antigen and plasminogen activator inhibitor.

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits plasminogen activator (PA) activity and reveals the presence of a specific PA inhibitor (PAI-1). To determine whether the hormonal inhibition of PA activity reflects a decrease in the amount of PA or an increased amount of the inhibitor, or both, we have assayed PA and PAI-1 immunologically. HTC PA was determined to be entirely of the tissue type (tPA), and both free and complexed antigen was quantified by a RIA using rabbit antirat tPA, with rat insulinoma tPA as tracer and standard. PAI-1 was quantified by a Western blot assay using rabbit anti-HTC PAI-1 antibody and purified HTC PAI-1 as standard. Under conditions in which dexamethasone inhibited PA activity by 90%, there was no decrease in the cellular content of tPA antigen. Paradoxically, dexamethasone increased tPA antigen approximately 1.5-fold. Under these same conditions, dexamethasone increased PAI-1 antigen 4- to 5-fold. We conclude that the glucocorticoid inhibition of tPA activity in HTC cells is not secondary to a decrease in the amount of tPA but is secondary to the induction of a specific PA inhibitor.

Animals↗
PubMed1996

Interaction of tissue plasminogen activator inhibitor with cell surface guanidinobenzoatase and urokinase plasminogen activator.

This study employs fluorescent inhibitor molecules to detect both cell surface proteases and their receptor sites on colonic carcinoma cells. Present studies are concerned with the interactions of the tumour associated proteases, guanidinobenzoatase (GB) and plasminogen activators (PAs) with PAs inhibitor type 1 (PAI-1). The active enzymes on the cell surfaces in frozen sections of human colonic carcinoma tissue were located by staining with two active site directed fluorescent inhibitors, 9-aminoacridine (9-AA) and Rhodamine labelled PAI-1 (Rh-PAI-1), followed by fluorescence microscopy. Fibrin treated sections, which now lack GB but have receptor proteins for GB, fail to bind 9-AA and Rh-PAI-1. When these fibrin-treated sections were incubated with purified colonic carcinoma GB and u-PA, both enzymes were bound to the tumour cells in these sections and subsequent challenging with fluorescent probes for GB resulted in bright fluorescence under appropriate microscopic conditions. On the other hand when fibrin treated sections were incubated with t-PA, followed by challenging with Rh-PAI-1, no red fluorescence was observed. It is suggested that the GB and u-PA have similar specific binding sites which can recognise and bind to the receptors on tumour cells in fibrin-treated sections, but t-PA has no such binding site and fails to recognise the cell surface receptors for GB. These GB-receptors may have a possible role in the regulation of GB and u-PA activity during tumour cell invasion and metastasis.

Aminacrine↗
PubMedDate not supplied

Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma.

The urokinase-type plasminogen activator (uPA) and its inhibitors type 1 (PAI-1) and type 2 (PAI-2) are considered to have a key role in the process of invasion and metastasis. We investigated the differences in uPA, PAI-1 and PAI-2 concentrations in primary cutaneous melanoma and normal skin and correlations with well-established melanoma prognostic factors. The study was performed on 43 patients (19 men, 24 women; mean age 57 years) with histologically confirmed primary melanomas <1.5 mm thick. The uPA concentrations were determined in 36 pairs of triton extracts, and the PAI-1 and PAI-2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples (matched pairs). The uPA, PAI-1 and PAI-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Significantly higher concentrations of both uPA and PAI-1 were measured in melanomas than in normal surrounding skin (uPA: 1.08 vs 0.48 ng/mg total protein (mgp), p<0.001; PAI-1: 14.07 vs 2.07 ng/mgp, p<0.001). The melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly (p<0.05) with normal skin (r=0.73, 0.54, 0.38 respectively). The uPA concentrations positively correlated with those of PAI-1 measured in melanomas (r=0.45, p<0.01). PAI-1 values were significantly lower (p<0.001) in the melanomas of Breslow thickness < or =0.75 mm, Clark invasion 0.75 mm, Clark invasion of > or =II and < or =III, with microscopic ulceration and vascular invasion (22.25, 17.67, 27.67, 37.77, respectively). Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.

Adult↗
PubMed1990

Relationships between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1.

The relationships between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis time (ELT) were investigated with healthy volunteers' plasma. Turbidimetric clot lysis assay by the microtiter plate reader was utilized for ELT with a slight modification. Both tPA and PAI-1 showed the significant correlation with ELT. tPA had a significantly positive, not negative, correlation with ELT (R = 0.387, p less than 0.001). Higher correlation coefficients (R = 0.580, p less than 0.001 and R = 0.599, p less than 0.001) were obtained between ELT and total PAI-1 or free PAI-1 than tPA or tPA-PAI-1 complex (R = 0.427, p less than 0.001). The positive correlation was also obtained between tPA and PAI-1. These data suggest that PAI-1 is a highly important factor for ELT, especially, the amounts of free PAI-1 being the key factor to determine the ELT, which can represent the potential activity of the fibrinolytic system.

Adult↗
PubMed1991

Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation.

Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t-PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.

Disseminated Intravascular Coagulation↗