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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peculiarly fibrinous nature of bovine acute lung injury due to infection with Pasteurella haemolytica A1 suggests an imbalance between leukocyte-directed procoagulant and profibrinolytic influences in the inflamed bovine lung. Calves with experimental pneumonia produced by intratracheal inoculation with P. haemolytica A1 developed acute locally extensive cranioventral fibrinopurulent bronchopneumonia. Pulmonary alveolar macrophages (PAM) recovered by segmental lavage from affected lung lobes were 30 times more procoagulant than PAM obtained from unaffected lung lobes and 37-fold more procoagulant than PAM from control calf lungs. Unlike the enhancement of procoagulant activity, profibrinolytic activity (plasminogen activator amidolysis) of total lung leukocytes (PAM and plasminogen activator neutrophils [PMN]) was decreased 23 times in cells obtained from affected lung lobes and also was decreased four times in cells obtained from unaffected lobes of infected animals. This marked imbalance in cellular procoagulant and fibrinolytic activity probably contributes significantly to enhanced fibrin deposition and retarded fibrin removal. In addition, PAM from inflamed lungs were strongly positive for bovine tissue factor antigen as demonstrated by immunocytochemistry. Intensely tissue factor-positive PAM enmeshed in fibrinocellular exudates and positive alveolar walls were situated such that they were likely to have, in concert, initiated extrinsic activation of coagulation in the acutely inflamed lung. These data collectively suggest that enhanced PAM-directed procoagulant activity and diminished PAM- and PMN-directed profibrinolytic activity represent important modifications of local leukocyte function in bovine acute lung injury that are central to the pathogenesis of lesion development with extensive fibrin deposition and retarded fibrin removal.
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PMID:The role of leukocytes in the pathogenesis of fibrin deposition in bovine acute lung injury. 202 7

The potential importance of pleural fibrin deposition in the pathogenesis of pleural injury is supported by both clinical and experimental observations. We hypothesized that the local equilibrium between procoagulant and fibrinolytic activities is disrupted to favor fibrin deposition in exudative pleuritis. To test this hypothesis, we characterized procoagulant and fibrinolytic activities in pleural exudates from patients with pneumonia, lung cancer, or empyema and transudates from patients with congestive heart failure. Procoagulant activity was generally increased in exudative processes and was due mainly to tissue factor. All effusions contained antithrombin III and inhibited factor Xa and thrombin, but endogenous prothrombinase or thrombin activities were variably detected. Pleural fluid fibrinolytic activity was increased in congestive heart failure and was due to both tissue plasminogen activator and urokinase. Depressed fibrinolytic activity was found in pleural exudates despite increased concentrations of plasminogen, mainly glu-1-plasminogen, and was due to inhibition of plasminogen activation by plasminogen activator inhibitors 1 and 2 and of plasmin, in part by alpha 2-antiplasmin. Concentrations of PAI-1 in exudative pleural fluids were increased up to 913-fold, compared with normal pooled plasma. Exudative pleural effusions are characterized by increased procoagulant and depressed fibrinolytic activity, favoring fibrin deposition in the pleural space. The balance of these activities is reversed and favors fibrin clearance in congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities of pathways of fibrin turnover in the human pleural space. 206 28

Experiments were carried out to examine relationships between alveolar macrophage maturity and amounts of tissue factor (Clotting Factor III) in these cells under physiologic conditions and during immunologically induced pneumonitis. Using discontinuous density gradient centrifugation, alveolar macrophages from healthy rabbits were rapidly isolated into five subpopulations at different stages of maturation, as demonstrated by morphologic and morphometric evaluation. Very large amounts of tissue factor activity were found in fully mature cells that were purified in the lowest density subpopulation and assayed without preliminary in vitro stimulation or culture. In the remaining four subpopulations of increasing density, amounts of tissue factor were found to progressively diminish in direct correlation with declines of cell maturity. These differences at mean levels were as great as 35-fold. In addition, blood monocytes had less than 1/219 and less than 1/6 of the activity of the fully mature and the least mature subpopulations, respectively. After 16 h culture of the five isolated subpopulations in the absence of lymphokines or of significant numbers of lymphocytes, tissue factor activity increased in inverse correlation with the preincubation stage of cell maturity (2,387 and 109% in the least mature and most mature subpopulations, respectively). These increases required protein synthesis and were accompanied by morphologic and morphometric changes which indicated cellular maturation during the period of tissue factor activity generation in vitro, thus further demonstrating relationships between macrophage maturity and tissue factor content. In additional experiments, direct correlations between cell maturity and tissue factor activity content were also found in activated alveolar macrophage populations from rabbits with Bacillus Calmette Guering (BCG)-induced granulomatous pneumonitis. However, as compared with controls, the BCG populations had increased total amounts of tissue factor activity due to the presence of large numbers of mature alveolar macrophage forms that had high levels of the procoagulant. Thus, tissue factor activity in alveolar macrophages is a marker of cellular maturation in vivo and in vitro. Increased amounts of this initiator of the extrinsic clotting pathway, as found in alveolar macrophage populations from animals with granulomatous pneumonitis induced by BCG hypersensitivity, suggest that alveolar macrophage tissue factor may contribute to the pathology of immune lung diseases.
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PMID:Tissue factor activity. A marker of alveolar macrophage maturation in rabbits. Effects of granulomatous pneumonitis. 637 26

Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation. We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS. From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18. Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity. Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS. C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge. Peptide #36 also blocked the LPS-induced lethality. These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains). Both peptides inhibited TF- and Xa-induced plasma clotting. Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin). In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin). Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities. The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini. This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7. These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.
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PMID:Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities. 783 55

Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohistochemistry and compared the results with those from patients who had interstitial pneumonia associated with systemic sclerosis (IP-SSc) and idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP). Expression of TF-mRNA was also assessed, using in situ hybridization with a digoxigenin-labeled cRNA probe. In patients with IPF, IP-SSc, and idiopathic BOOP, the TF antigen was positively stained in type II pneumocytes and in some alveolar macrophages. The fibrin antigen was stained in the type II pneumocytes and the adjacent area. Tissue factor-mRNA was expressed in the type II pneumocytes and in some alveolar macrophages. Neither TF antigens nor TF-mRNA were detected in the normal lung. These results indicate that type II pneumocytes are a major source of TF, suggesting that TF production in these cells is closely related to fibrin deposition in the lungs of people with these diseases.
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PMID:Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. 927 50

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.
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PMID:Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. 1067 85

The mesothelial lining of the pleura and malignant mesothelioma promote fibrin deposition in pleural injury or neoplasia via expression of tissue factor (TF). It was hypothesized that these cells might also regulate intrapleural coagulation by elaborating TF pathway inhibitor (TFPI). TFPI activity and antigen in pleural fluids were assayed from patients with congestive heart failure (CHF), pneumonia, empyema, metastatic pleural cancer and malignant mesothelioma. The authors also assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as TFPI activity and antigen by human pleural mesothelial cells, malignant mesothelioma cells (MS-1 cell line) and human lung fibroblasts. Immunohistochemical analyses of normal, fibrotic, and neoplastic pleura were performed to determine whether TFPI antigen was expressed in vivo. The study revealed that TFPI was present in transudates from patients with CHF and exudative pleural effusions from patients with pneumonia, empyema or pleural carcinoma. TFPI mRNA, activity and antigen were expressed by pleural mesothelial cells, MS-1 cells and lung fibroblasts. Cytokines and serum stimulated a significant early increase in TF mRNA levels with minimal enhancement of TFPI mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and neoplastic pleural tissues. The current observations indicate that tissue factor pathway inhibitor is locally expressed in pleural disease, but that it does not prevent the development of a prothrombotic environment favouring local fibrin deposition in pleural inflammation or cancer.
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PMID:Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells. 1088 26

Inflammatory reaction is a classical feature of radiation exposure, and pneumonitis is a dose-limiting complication in the handling of hematological disorders treated with total-body irradiation. In the present study, we first evaluated the inflammatory response in C57BL6/J mice exposed to lethal doses of gamma rays treated with antibiotics or not. Both interleukin 6 and KC (also known as Gro1) were increased in the plasma 10 to 18 days after radiation exposure, independent of bacterial infection, whereas fibrinogen release was linked to a bacterial infection. Furthermore, both Il6 and KC were increased in the lungs of irradiated mice. Our second objective was to characterize the endothelial cell changes in the lungs of total-body-irradiated mice. For this purpose, a quantitative RT-PCR was used to determine the expression of genes involved in inflammatory and coagulation processes. We found that the adhesion molecules P-selectin and platelet endothelial cell adhesion molecule 1 were up-regulated, whereas E-selectin remained unchanged. Tissue factor expression was up-regulated as well, and thrombomodulin gene expression was down-regulated. The investigation by immunohistochemistry of adhesion molecules confirmed the increase in the basal expression of both P-selectin and platelet endothelial cell adhesion molecule 1 on pulmonary endothelial cells. All together, our results suggest the involvement of endothelial cells in the development of radiation-induced inflammatory and thrombotic processes.
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PMID:Inflammatory reaction and changes in expression of coagulation proteins on lung endothelial cells after total-body irradiation in mice. 1464 Jul 83

Severe infection is associated with profound alterations in the systemic haemostatic balance, with activation of coagulation and suppressed fibrinolysis. Within the alveolar compartment, similar disturbances have been described during pulmonary inflammation. The current authors investigated whether local haemostasis was influenced during ventilator-associated pneumonia (VAP). In five patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained from both the infected site (as identified on chest radiograph) and the contralateral noninfected lung (with no clinical or radiographic abnormalities). Markers for coagulation and fibrinolysis were compared between infected and noninfected lungs. A total of 10 healthy volunteers and 10 mechanically ventilated patients without pneumonia served as controls. Strong activation of coagulation (high levels of thrombin-antithrombin complexes, soluble tissue factor and factor VIIa) was detected in BALF from infected lungs, compared with that from noninfected lungs and controls. Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1. In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection.
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PMID:Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection. 1551 73

Pneumonia is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. To determine the effect of lipopolysaccharide (LPS) on the hemostatic balance in the human lung, six healthy subjects inhaled nebulized LPS or saline in a randomized cross-over study and bronchoalveolar lavage fluid was obtained six hours thereafter. LPS induced soluble tissue factor and thrombin-antithrombin complexes and inhibited plasminogen activator activity in BALF. Additionally plasminogen activator inhibitor type 1 production was upregulated after LPS inhalation. LPS also elicited local activation of neutrophils (release of elastase, myeloperoxidase and bactericidal/permeability increasing protein) and secretion of interleukin (IL)-6 and IL-8. Inhalation of LPS by healthy humans reproduces major features of the procoagulant response to inflammatory and infectious lung diseases and may be used as a novel model to evaluate pathogenetic mechanisms and new interventions.
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PMID:Activation of coagulation and inhibition of fibrinolysis in the lung after inhalation of lipopolysaccharide by healthy volunteers. 1596 85


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