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P Montemurro

Publications and source records attributed to P Montemurro.

At least 19 recordsLinked to original sources
PubMed2001

Helicobacter pylori neutrophil-activating protein stimulates tissue factor and plasminogen activator inhibitor-2 production by human blood mononuclear cells.

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor that activates phagocytic NADPH-oxidase. The effect of HP-NAP on the production of tissue factor (TF), plasminogen activator inhibitor-2 (PAI-2), and urokinase-type plasminogen activator (u-PA) by human blood mononuclear cells (MNC) was evaluated by using functional and immunological assays and mRNA analysis. HP-NAP induced time- and dose-dependent increases in TF and PAI-2, with a maximal effect at 300 nmol/L (>15-fold increase in antigens). No changes in u-PA were observed. When whole bacteria were used, an H. pylori mutant lacking HP-NAP was significantly less active than the wild-type strain. MNC from a patient with chronic granulomatous disease behaved as do normal cells, which indicates that HP-NAP effects can occur independently of NADPH-oxidase. HP-NAP, by inducing the coordinate expression of cell procoagulant and antifibrinolytic activities, might favor fibrin deposition and contribute to the inflammatory reaction of gastric mucosa elicited by H. pylori.

Bacterial Proteins↗
PubMed2001

Nicotine effects on polymorphonuclear cell apoptosis and lipopolysaccharide-induced monocyte functions. A possible role in periodontal disease?

Apoptosis provides a mechanism for clearance of unwanted cells in a variety of situations in which programmed or physiological cell death occurs; but the premature death of defensive cells could promote infection, inflammation and concomitant disease. We detected high values of apoptosis in polymorphonuclear cells (PMN) elicited from crevicular sulci of smokers affected by adult periodontitis. To learn more about the effects of nicotine on the periodontal environment, we studied its ability to modulate the apoptosis of two phagocytic lines, PMN and mononuclear cells, which are continuously recruited from gingival vessels to prevent or control plaque extension. Brief exposure of PMN to nicotine concentrations ranging from 0.01 to 0.3% shortened, in a dose-dependent relationship, the lag culture time required to observe at fluorescent microscopy the morphological traces of apoptosis. These observations were confirmed by specific tools of apoptosis: DNA fragmentation on gel electrophoresis and expression of the apoptosis-signaling receptor Fas/Apo-1. The apoptotic effect excited by nicotine on these first line defensive cells may be an important feature of the pathogenesis of periodontal disease. As for mononuclear leukocytes, nicotine was unable to induce apoptotic modifications on cells observed up to 72 h culture time, but the drug inhibited IL-1beta release and procoagulant activity (PCA) expression. The conflicting role played by these lipopolysaccharide (LPS)-induced monocyte functions in the inflammatory process is a further intrigue in the mechanism by which nicotine compromises the oral health.

Apoptosis↗
PubMed1999

Retinoic acid stimulates plasminogen activator inhibitor 2 production by blood mononuclear cells and inhibits urokinase-induced extracellular proteolysis.

Retinoids have been shown to modulate several functions of mononuclear phagocytes. We investigated the in vitro effect of all-trans-retinoic acid (ATRA) on the production of two major fibrinolytic components, urokinase-type plasminogen activator (u-PA) and PA inhibitor 2 (PAI-2), by human blood mononuclear cells (MNC). ATRA caused a dose-dependent (range 0.01-10 microM) accumulation of PAI-2 antigen and activity into the cell culture medium, with a maximal increase (about 5-fold over control) at a concentration of 1-10 microM. Similarly, a dose-dependent increase in PAI-2 antigen was observed in cell extracts upon ATRA stimulation. Northern blot analysis showed a parallel increase in the amount of PAI-2 mRNA in ATRA-treated cells. Time-course experiments with 1 microM ATRA showed enhanced PAI-2 mRNA expression as early as 2 h, reaching a maximum at 4-6 h and then declining at 18-24 h, and a time-dependent increase in PAI-2 antigen in the cell culture medium. At variance with PAI-2, u-PA was not influenced by the drug. To establish whether ATRA-induced changes influenced the fibrinolytic process, we evaluated the effect of MNC stimulated with ATRA on u-PA-induced degradation of diluted plasma clots. ATRA-treated cells markedly inhibited clot lysis induced by low concentrations of u-PA. The effect was due to enhanced extracellular PAI-2 accumulation since it was observed with conditioned medium from ATRA-treated cells; it was abolished by the addition of neutralizing anti-PAI-2 antibodies and was negligible when single-chain t-PA was used instead of u-PA. Since monocyte/macrophage-mediated, plasminogen-dependent extracellular proteolysis has been proposed as an important mechanism of tissue damage in several inflammatory states, our findings might contribute to better explain the anti-inflammatory properties of retinoids.

Blotting, Northern↗
PubMed1996

Effect of Helicobacter pylori lipopolysaccharide (LPS) and LPS derivatives on the production of tissue factor and plasminogen activator inhibitor type 2 by human blood mononuclear cells.

Different Helicobacter pylori lipopolysaccharides (LPSs) and LPS-derivatives were studied for their ability to induce the production of procoagulant activity (PCA) and plasminogen activator inhibitor type 2 (PAI-2) by human blood mononuclear leukocytes. Smooth (S)- and rough (R)-form LPSs caused a similar increase in cell-associated PCA (tissue factor) and PAI-2 antigen release. Both effects were potentiated by fetal bovine serum via a CD14-mediated mechanism. The potency of H. pylori LPSs was approximately 1000-fold lower than that of Salmonella typhimurium LPSs. When H. pylori LPS derivatives (dephosphorylated R-LPS, S-lipid A, and R-lipid A) were used, PCA and PAI-2 production were markedly reduced. R-lipid A was approximately 4-fold less efficient than S-lipid A. These findings suggest that the induction of monocyte tissue factor and PAI-2 by H. pylori LPS is influenced by the lipid A structure and modulated by the core oligosaccharide and that phosphate groups present in both regions may play an important role.

Helicobacter Infections↗
PubMed1995

Blood and tissue fibrinolytic profiles in patients with colorectal carcinoma.

In patients with colorectal cancer, profound alterations of the plasminogen activator system have been described at the tumor level, but conflicting results have been obtained for fibrinolytic parameters in plasma. Components of the fibrinolytic system, including tissue-type and urokinase-type plasminogen activators and their inhibitors type 1 and 2, were measured in tissue and/or plasma from 41 patients with colorectal cancer and in 40 controls. Procoagulant activity of freshly isolated mononuclear cells (basal activity) and the procoagulant activity and fibrinolytic proteins produced by the cells after incubation for 18 h without exogenous stimulation were also evaluated. Malignant tissue extracts had significantly higher levels of urokinase-type plasminogen activator and plasminogen activator inhibitor-1, but lower levels of tissue-type plasminogen activator than normal mucosa. Plasminogen activator inhibitor-1 alone was higher in advanced (Dukes' stages C + D) than limited (B) tumors. Plasminogen activator inhibitor-2 was not different in malignant tissue and normal mucosa. Plasma levels of plasminogen activator inhibitor-1 antigen were significantly increased in cancer patients compared with controls, but there were no differences in tissue-type and urokinase-type plasminogen activator, in plasminogen activator inhibitor-2, and D-dimer levels. Intra-patient analysis revealed no significant correlation between tumor and plasma levels of plasminogen activators or type 1 inhibitor. Tissue-type plasminogen activator, but not the urokinase type or inhibitor type 1, was higher in venous than in arterial blood collected at the tumor site during surgery. Basal procoagulant activity of mononuclear cells and the procoagulant activity and inhibitor type-2 produced by the cells after short-term culture were comparable in patients and controls. These findings indicate that, at least in our patients with colorectal cancer, the profound changes occurring at tumor level are barely detectable in the blood. Thus, the clinical relevance of plasma fibrinolytic parameters, especially urokinase-type plasminogen activator antigen, as tumor markers in colorectal cancer remains to be established.

Adult↗
PubMed1995

Cultured human mesangial cells produce both type 1 and type 2 plasminogen activator inhibitors.

Cultured human mesangial cells (HMC) derived from normal kidneys have been shown to synthesize tissue-type plasminogen activator (t-PA) and excess amounts of PA inhibitor type 1 (PAI-1). Conflicting results have been obtained concerning the production of urokinase-type PA (u-PA) and efforts to show PA inhibitor 2 (PAI-2) met with failure. We evaluated the fibrinolytic profile of cultured HMC lines obtained from 12 patients with renal carcinoma and one cadaveric kidney donor. Subconfluent cells (third passage) were incubated overnight in serum-free medium. t-PA, u-PA, PAI-1 and PAI-2 antigens were assayed by ELISA methods and PA and PAI activities by amidolytic methods both in conditioned medium (CM) and cell extracts (CE). Besides PAI-1, PAI-2 antigen was detected in all but one HMC lines. At variance with the former, which was largely released in the culture medium, PAI-2 was mainly cell-associated. t-PA antigen was found in all but two cell lines while u-PA antigen was detected in relatively high concentrations in 8 cell lines. PA activity, identified as u-PA by functional and immunological criteria, was measured in CM of six of the eight u-PA producing cell lines, whereas PAI activity was undetectable or very low in CM of all cell lines, suggesting that PAI-1 was largely inactive. Functional assays of cell extracts demonstrated the presence of PA activity, again identified as u-PA, only in samples (five lines) containing u-PA antigen in excess over PAI-2. PAI activity was found instead in the extracts in which the inhibitor was higher than the activator (six lines) and was identified as PAI-2, as it inhibited u-PA but not single-chain t-PA and was neutralized by a polyclonal anti-PAI-2 antibody. The heterogeneous fibrinolytic pattern of HMC lines was confirmed by mRNA analysis of three representative lines. Results were similar when HMC lines at passage five were used, except that the u-PA content was significantly reduced both in CM and CE. These findings indicate that the fibrinolytic profile of cultured HMC is more complex than previously reported. The production of large amounts of PAI-2 may represent an additional control mechanism of proteinase activity.

Blotting, Northern↗
PubMed1994

Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma.

Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin's, 4 Hodgkin's) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37 degrees C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients' mononuclear cells after incubation for 20 h at 37 degrees C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p < 0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p < 0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer were markedly increased in the patient's group (p < 0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.

Adolescent↗
PubMed1993

Enhanced endothelial tissue factor but normal thrombomodulin in endotoxin-treated rabbits.

Exposure of cultured endothelial cells to bacterial endotoxin induces an enhancement of cell procoagulant activity (PCA) and a simultaneous reduction of thrombomodulin activity (TM). We evaluated the effect of endotoxin on the expression of both endothelial PCA and TM in vivo, in rabbits. Animals were given a single i.v. injection of endotoxin (E. coli 0111:B4 LPS, W, 10-200 micrograms/kg); the thoracic aorta was harvested after 2 or 4 hours and placed in an ad hoc device to expose the endothelial surface only. Endotoxin treatment resulted in a dose-dependent increase of endothelial PCA (p < 0.001, at 100 micrograms/kg or more), which was totally dependent on factor VII and thus identified as tissue factor. In contrast, endothelial TM activity, as measured by the rate of thrombin-induced protein C activation, was similar in control and endotoxemic rabbits, even when the animals were given two injections (50 micrograms/kg, 24 h apart), or a continuous infusion (40 micrograms/kg/h during 4 hours) of endotoxin. To explore the effect of endotoxin on TM activity at the microcirculation level, we measured the extent of protein C activation in vivo, induced by a continuous infusion of low doses of thrombin (1 NIH U/kg/min for 60 min). Again, endotoxin administration was not associated with significant changes in TM-dependent protein C activation, as assessed by the anticoagulant activity present in a barium citrate plasma eluate obtained at the end of thrombin infusion. Although reduction of TM during persistent endotoxemia cannot be definitively excluded, our data support a major role of endothelial PCA in LPS-induced coagulative changes.

Animals↗
PubMed1991

Inhibitory effect of retinoids on the generation of procoagulant activity by blood mononuclear phagocytes.

Retinoids are known to modulate several functions of mononuclear phagocytes. We have studied the effect of retinyl acetate (RAc) and retinoic acid (RA) on the production of procoagulant activity (PCA) by human peripheral blood mononuclear cells stimulated with endotoxin (1 microgram/ml, 4 or 20 h at 37 degrees C). Both compounds caused a dose-dependent reduction in the expression of cell-associated PCA (from 86 to less than 10% of control in the range of concentration comprised between 0.1 and 100 microM). This effect was also observed when the cells were exposed to retinoids for 10 min and washed before challenge with endotoxin, indicating that it is rapid and irreversible. In contrast, incubation of RAc or RA for 3 h at 37 degrees C with cells that have been already stimulated with endotoxin (20 h at 37 degrees C) remained without influence on cell PCA. The inhibitory action of retinoids was also observed when monocyte-enriched (greater than 85%) preparations or highly purified monocyte-derived macrophages (greater than 99%) were used instead of whole mononuclear cells. BW755C, an inhibitor of cyclo-oxygenase and lipoxygenase, reversed the inhibitory effect of retinoids, whereas acetylsalycilic acid, an inhibitor of cyclo-oxygenase, was inactive, suggesting the involvement of a lipoxygenase product. The inhibition of monocyte/macrophage PCA production and the subsequent reduction of cell potential for fibrin deposition might represent one of the mechanisms whereby retinoids exert their antiinflammatory and immunomodulatory activities.

Blood Coagulation↗
PubMed1991

Retinoids inhibit the respiratory burst and degranulation of stimulated human polymorphonuclear leukocytes.

Retinoids exhibit a wide spectrum of activities, including antiinflammatory properties. We have investigated the effect of retinoic acid (RA) and retinyl acetate (RAc) on the production of reactive oxygen metabolites and the release of lysosomal enzymes by human polymorphonuclear leukocytes (PMN). Incubation of PMN with RAc or RA (1-100 microM) caused a dose-dependent inhibition (upto 90%) in O2- production and chemiluminescence induced by phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylanaline (fMLP), opsonized zymosan or ionophore A23187. Both retinoids (1-100 microM) also inhibited, in a dose-dependent way, degranulation induced by fMLP (upto 85% at the highest concentration of RA). These inhibitory effects appear irreversible, since they persist after the drugs are removed and the cells washed before stimulation. Inhibitors of cyclo-oxygenase activity such as acetylsalicyclic acid and indomethacin did not influence the effects of RAc. In contrast, BW755, an inhibitor of both cyclooxygenase and lipoxygenase, reversed the inhibitory action of RAc, suggesting that the effect of retinoids occurs possibly through the mediation of lipoxygenase products. The modulation of PMN oxidative metabolism and degranulation might help explain the antiinflammatory properties of retinoids.

Calcimycin↗
PubMed1991

Urinary procoagulant and fibrinolytic activity in human glomerulonephritis. Relationship with renal function.

Fibrin deposition in kidney is a common event in some forms of human and experimental glomerulonephritis, and is thought to result from local activation of blood coagulation and/or impaired removal by the fibrinolytic system. We studied the urinary procoagulant and fibrinolytic activities in 46 patients with renal disease (26 with IgA nephritis, 13 with other forms of glomerulonephritis and 7 with non-inflammatory kidney disease) and in 15 matched healthy subjects, as possible indicators of the coagulation-fibrinolysis balance in kidney. Procoagulant activity was slightly but not significantly increased in patients with serum creatinine levels higher than 1.5 mg/dl (group II) as compared with patients with normal creatinine (group I) and controls. It was identified as tissue factor by biological criteria (dependence on factor VII). Fibrinolysis studies showed that both plasminogen activator activity and urokinase antigen were significantly lower in group II than in group I patients and controls (P less than 0.0005). Reduced fibrinolytic activity in patients' urine was due to decreased excretion of urokinase since no inhibitor was detected by both fibrin autography and functional assay. No differences were found between patients and controls in plasma fibrinolytic activity, plasminogen activator inhibitor, and procoagulant activity of blood monocytes. The urinary changes in severe renal disease may reflect an unbalance of the coagulation-fibrinolysis equilibrium in kidney and might be of pathogenetic and clinical relevance.

Adolescent↗
PubMed1990

Unbalanced coagulation-fibrinolysis potential during L-asparaginase therapy in children with acute lymphoblastic leukaemia.

Treatment of acute lymphoblastic leukaemia (ALL) with L-asparaginase (L-asp) may be associated with thrombotic complications, but the pathogenetic mechanisms of thrombus formation and persistence remain unclear. We studied the procoagulant activity (PCA) of peripheral blood mononuclear cells and some components of the plasma fibrinolytic system in 10 children with ALL undergoing remission induction therapy which includes L-asp. Mononuclear cells obtained 14 days after starting L-asp treatment generated significantly higher amounts of PCA (identified as tissue factor) than cells isolated before the first dose of L-asp and 7 days after the cessation of L-asp administration (p less than 0.01). Augmented PCA coincided with an increase in the plasma D-dimer. The plasma levels of type 1 plasminogen activator inhibitor were found significantly elevated during L-asp therapy (p less than 0.05), whereas plasminogen levels were markedly decreased (p less than 0.05). These findings suggest that, during the course of L-asp treatment, the coagulation-fibrinolysis balance is shifted towards promotion of fibrin formation and deposition. Although it remains to be conclusively established whether L-asp per se or the concurrent administration of multiple chemotherapeutic agents is responsible for these changes, the latter could contribute to the thrombotic complications associated with remission induction therapy for ALL.

Asparaginase↗
PubMed1990

Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies.

Mononuclear phagocytes exhibit complex interactions with cancer cells and might contribute to fibrin formation associated with malignancy through the production of procoagulant activity (PCA). We have studied the PCA of peritoneal macrophages in 8 patients with advanced (stages III or IV) ovarian cancer and of macrophages from regional lymph nodes in 14 patients with limited (stages I or II) uterine cancer; peritoneal and lymph-node macrophages from patients with benign gynecological tumors were used as reference cell populations. In all patients, PCA of blood monocytes was also studied. Peritoneal and lymph-node macrophages obtained from patients with ovarian and uterine cancer, respectively, expressed far higher levels of basal PCA than the corresponding cell populations from patients with benign tumors (p less than 0.001). PCA of blood mononuclear cells from patients with ovarian, but not with uterine cancer, was significantly higher (p less than 0.001) than that of control cells. High levels of D-dimer, a specific product derived from plasmin-induced degradation of stabilized fibrin, were found in all ascitic fluids and in all plasma samples but one from patients with ovarian cancer. In contrast, all controls and all uterine cancer patients but one had normal plasma D-dimer. Our findings suggest that local activation of host macrophages for PCA production might contribute to fibrin formation within the tumoral mass. In advanced cancer, blood monocytes may also be activated to produce PCA and thus contribute to activation of intravascular coagulation and, possibly, to thrombo-embolic complications frequently associated with disseminated malignancy.

Aged↗
PubMed1990

Increased macrophage procoagulant activity but normal endothelial thrombomodulin in rabbits fed an atherogenic diet.

We have studied the procoagulant activity (PCA) of blood and spleen mononuclear phagocytes and the thrombomodulin activity of aortic segments in rabbits fed an atherogenic diet for 6 weeks as compared to rabbits fed a standard diet. Blood monocytes expressed negligible basal PCA (i.e., PCA measured immediately after cell isolation) both in treated and control rabbits. PCA induced by endotoxin in vitro was not different in the two groups. In contrast, dietary treatment resulted in a significant increase in the basal PCA of spleen cells (p less than 0.01). Moreover, the latter produced significantly more PCA than control cells (p less than 0.002) in response to endotoxin in vitro. The thrombomodulin activity associated with aortic endothelium was not different in the two groups of animals despite the presence of visible fatty streaks on the aortic endothelium of treated rabbits. When rabbits were given a single injection of endotoxin, spleen mononuclear phagocytes harvested 60 min after the injection from treated animals expressed three times more PCA (p less than 0.01) than did cells from controls. In all instances PCA was identified as tissue factor. Endotoxin injection did not affect the thrombomodulin activity of thoracic aorta from both control and diet groups. It is suggested that dietary fats may cause early functional changes in mononuclear phagocytes that lead to an increased PCA production both in vivo and in vitro. These data may be relevant to an understanding of the role of monocytes-macrophages in the pathogenesis of atherosclerosis.

Animals↗
PubMed1989

Increased procoagulant activity of peripheral blood monocytes in human and experimental obstructive jaundice.

We studied the procoagulant activity of peripheral blood monocytes in 41 patients with severe obstructive jaundice and in 27 nonjaundiced control patients using a one-stage clotting assay. Mononuclear cells from jaundiced patients, tested immediately after isolation, expressed low levels of procoagulant activity, which were, however, significantly higher than in cells from controls (p less than 0.01). In addition, after incubation in short-term cultures with and without endotoxin, these cells generated more procoagulant activity than did the control ones (p less than 0.001). No significant difference in procoagulant activity was found between patients with and without malignancy in either group. The relief of biliary obstruction resulted in the reduction of both serum bilirubin levels and monocyte procoagulant activity. Endotoxin-induced monocyte procoagulant activity was about threefold higher in the jaundiced patients who died than in the survivors (p less than 0.001). In rabbits made icteric by bile duct ligation and separation (15 days), the endotoxin-induced monocyte procoagulant activity was markedly increased as compared with sham-operated animals (p less than 0.005). In all instances, procoagulant activity was identified as tissue factor. The increased capacity of mononuclear phagocytes to produce procoagulant activity might help explain the activation of blood coagulation in severe obstructive jaundice.

Adult↗
PubMed1988

Aggregation of human peripheral blood mononuclear cells by calcium ionophore A23187. Comparison with the aggregation of platelets and defective response in Glanzmann's thrombasthenia.

Following exposure to calcium ionophore A23187, washed peripheral blood mononuclear cells (MNC) aggregated and formed thromboxane, like platelets. However, while aspirin strongly inhibited platelet aggregation and thromboxane formation, it had a little effect on the aggregation of MNC. In about 50% of the samples studied, aggregation of MNC was associated with the secretion of ATP. However studies in which exogenous ATP or ADP were used, suggested that the aggregation of MNC is independent of the secretion of nucleotides. MNC from 2 thrombasthenic patients failed to aggregate and bound 9-10 fold less radiolabelled fibrinogen than those from normals when challenged with A23187. However, fibrinogen, which plays a major role in the aggregation of platelets, did not appear to be involved in the aggregation of MNC. A differing behavior of these two types of cells was also found when the effect of plasma was studied on the aggregation response to A23187. Indeed, citrated plasma greatly enhanced the aggregation of platelets while it suppressed the response to MNC. This inhibitory effect of plasma was not detected when heparinized plasma was substituted for citrated plasma. We conclude that the aggregation of MNC in response to A23187 does not involve basic events known to play a major role in the aggregation of platelets. The response to A23187 may be an important probe for understanding basic mechanisms and pathophysiological significance of the aggregation of MNC.

Adult↗
PubMed1988

Treatment with cyclosporin A does not affect macrophage procoagulant activity and plasminogen activator inhibitor in mice.

Using a mouse model, we have investigated the in vivo effect of cyclosporin on macrophage procoagulant activity and on plasma levels of plasminogen activator inhibitor. Procoagulant activity of peritoneal macrophages was studied after treatment of mice with different regimens of cyclosporin (10 to 100 mg/kg body weight) for seven days. No significant difference was found between treated and control animals in both basal procoagulant activity and procoagulant activity generated during short-term culture in the absence or in the presence of endotoxin. These findings are in striking contrast with in vitro experiments showing that cyclosporin induced a significant increase in procoagulant activity when added to peritoneal macrophages from normal animals before challenge with endotoxin (p less than 0.01). Plasma levels of plasminogen activator inhibitor in cyclosporin-treated mice were not different from those of controls. It is suggested that factors other than monocyte-macrophage procoagulant activity or plasminogen activator inhibitor may be important for the postulated 'prothrombotic' action of cyclosporin.

Animals↗