fibrin and Lung-Diseases

Fibrinogen is a unique protein that is converted into an insoluble fibrin in a single enzymatic event, which is a characteristic feature of fibrinogen due to its susceptibility to fibrinolytic degradation and dissolution. Although thrombosis is a result of activated blood coagulation, no explanation is being offered for the persistent presence of fibrin deposits in the affected organs. A classic example is stroke, in which the thrombolytic therapy is effective only during the first 3-4 h after the onset of thrombosis. This phenomenon can now be explained in terms of the modification of fibrinogen structure induced by hydroxyl radicals generated during the period of ischemia caused, in turn, by the blocking of the blood flow within the obstructed vessels. Fibrinogen modification involves intra-to intermolecular disulfide rearrangement induced by the reductive power of hydroxyl radicals that result in the exposition of buried hydrophobic epitopes. Such epitopes react readily with each other forming linkages stronger than the peptide covalent bonds, thus rendering them resistant to the proteolytic degradation. Also, limited reduction of human serum albumin (HSA) generates hydrophobic polymers that form huge insoluble complexes with fibrinogen. Consequently, such insoluble copolymers can be deposited within the circulation of various organs leading to their dysfunction. In conclusion, the study of protein hydrophobic interactions induced by a variety of nutritional and/or environmental factors can provide a rational explanation for a number of pathologic conditions including cardiovascular, neurologic, and other degenerative diseases including cancer.

Topics: Animals; Arthritis; Cardiovascular Diseases; Diabetes Mellitus; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hydrophobic and Hydrophilic Interactions; Kidney Diseases; Lung Diseases; Models, Biological; Neoplasms; Nervous System Diseases; Polymerization; Protein Interaction Domains and Motifs; Serum Albumin, Human; Solubility; Thrombosis

Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.

Topics: Anemia; Bronchoscopy; Capillaries; Diagnosis, Differential; Dyspnea; Erythrocytes; Fibrin; Hemoptysis; Hemorrhage; Hemosiderin; Humans; Immunosuppressive Agents; Lung; Lung Diseases; Necrosis; Neutrophils; Pulmonary Alveoli; Pulmonary Embolism; Thoracoscopy; Vasculitis

Topics: Animals; Clinical Enzyme Tests; Coronary Disease; Diagnosis, Differential; Dogs; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Hypertension; Lung Diseases; Myocardial Infarction; Pulmonary Embolism; Solubility; Thrombophlebitis

Topics: Aging; Animals; Cholesterol; Fatty Acids; Fibrin; Heparin; Humans; Hyperlipidemias; Lipase; Lipid Metabolism; Lipidoses; Lipoprotein Lipase; Lung; Lung Diseases; Macrophages; Phagocytosis; Phospholipids; Silicosis

Here we report the antithrombotic functions of pyrimidinethiol-capped gold nanoparticles (Au_DAPT NPs). They can prolong coagulation parameters when injected intravenously in normal mice. Applied in two typical thrombosis models, mice tail thrombosis and pulmonary thromboembolism, gold NPs can inhibit both thrombosis and improve the survival rates of mice tremendously, without increasing the bleeding risk. The anticoagulant mechanisms include inhibiting the platelet aggregation as well as interfering with thrombin and fibrin generation.

Topics: Animals; Anticoagulants; Blood Coagulation; Blood Platelets; Fibrin; Fibrinolytic Agents; Gold; Hemorrhage; Lung Diseases; Male; Metal Nanoparticles; Mice; Pyrimidines; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds; Thrombin; Thrombosis; Whole Blood Coagulation Time

We explored novel functions of tenascin-C by comparing mouse embryonic fibroblasts (MEFs) proficient or deficient in tenascin-C expression. Transcript profiling analysis identified tissue plasminogen activator (tPA) as the most consistently over-expressed gene in all tenascin-C deficient MEFs. This was confirmed by real-time PCR as well as by protein expression analysis. In agreement with these observations, tenascin-C deficient MEFs had an increased capacity to digest fibrin in situ. Consistently, tenascin-C expression in vivo was found to correlate with fibrin deposition in several diseases associated with tenascin-C overexpression such as fibrosis, asthma and cancer. In conclusion, the present study suggests a new role of tenascin-C as a regulator of the fibrinolytic system.

Topics: Animals; Blotting, Western; Carcinoma, Squamous Cell; Down-Regulation; Embryo, Mammalian; Female; Fibrin; Fibrinolysin; Fibroblasts; Gene Expression Profiling; Head and Neck Neoplasms; Humans; Immunohistochemistry; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Tenascin; Tissue Plasminogen Activator

Assessing state of various hemostasis levels in patients having pulmonary diseases caused by dust, in accordance with respiratory failure severity, enables to diagnose early changes confirming hypoxia. The most reliable parameters are changes in vascular and platelet hemostasis and in fibrinolysis system.

Topics: Biomarkers; Bronchitis; Disease Progression; Early Diagnosis; Fibrin; Hemostasis; Humans; Hypoxia; Lung Diseases; Middle Aged; Occupational Exposure; Particulate Matter; Platelet Function Tests; Respiratory Insufficiency; Thrombin

Administration of inhaled nitric oxide (iNO) is a potential therapeutic strategy to prevent bronchopulmonary dysplasia (BPD) in premature newborns with respiratory distress syndrome. We evaluated this approach in a rat model, in which premature pups were exposed to room air, hyperoxia, or a combination of hyperoxia and NO (8.5 and 17 ppm). We investigated the anti-inflammatory effects of prolonged iNO therapy by studying survival, histopathology, fibrin deposition, and differential mRNA expression (real-time RT-PCR) of key genes involved in the development of BPD. iNO therapy prolonged median survival 1.5 days (P = 0.0003), reduced fibrin deposition in a dosage-dependent way up to 4.3-fold (P < 0.001), improved alveolar development by reducing septal thickness, and reduced the influx of leukocytes. Analysis of mRNA expression revealed an iNO-induced downregulation of genes involved in inflammation (IL-6, cytokine-induced neutrophilic chemoattractant-1, and amphiregulin), coagulation, fibrinolysis (plasminogen activator inhibitor 1 and urokinase-type plasminogen activator receptor), cell cycle regulation (p21), and an upregulation of fibroblast growth factor receptor-4 (alveolar formation). We conclude that iNO therapy improves lung pathology and prolongs survival by reducing septum thickness, inhibiting inflammation, and reducing alveolar fibrin deposition in premature rat pups with neonatal hyperoxic lung injury.

Topics: Administration, Inhalation; Animals; Animals, Newborn; Antioxidants; Bronchoalveolar Lavage Fluid; Cell Cycle; Fibrin; Fibrinolysis; Gene Expression Regulation; Lung; Lung Diseases; Nitric Oxide; Pneumonia; Proteins; Pulmonary Alveoli; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Survival Analysis

Intraalveolar fibrin formation is a consistent finding in acute inflammatory and chronic interstitial lung disease. Polymerization of fibrin in the presence of pulmonary surfactant results in far-reaching incorporation of the hydrophobic surfactant compounds into the growing fibrin matrix, with loss of surface activity, altered fibrin structure and reduced susceptibility of the clot to fibrinolysis. For specific targeting of such alveolar fibrin, we designed a hybrid molecule consisting of the catalytic domain of urokinase (B-chain) and the hydrophobic surfactant protein B (SP-B), termed SPUC. The urokinase B-chain, obtained by limited reduction of human two-chain-urokinase (u-PA) and subsequent affinity purification, was chemically coupled to SP-B in a semi-organic solvent system using a hetero-bifunctional crosslinker. Purification of the chimeric proteins included reversed phase and cation exchange chromatography. SDS-PAGE and Western Blotting with immunostaining were employed for biochemical characterization of the conjugate. Chromogenic substrate assays, (125)I-based fibrin plate assays, active site titration and surface tension measurements (pulsating bubble surfactometer) were performed to analyze the specific fibrinolytic activity of the conjugate and its surface activity. SPUC was found i) to be assembled stoichiometrically in a 1: 1 fashion (SP-B: u-PA), ii) to fully retain the biophysical activity as compared to native SP-B and iii) to also retain the fibrinolytic activity. SPUC was 2-3 fold more effective in lysis of surfactant containing clots and 5-fold more resistant against plasminogen activator 1 (PAI-1) as compared to the native u-PA. We conclude that urokinase and SP-B can be chemically crosslinked, thereby yielding a fibrinolytic enzyme suitable for targeting alveolar fibrin.

Topics: Chromogenic Compounds; Cross-Linking Reagents; Drug Design; Drug Stability; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Lung Diseases; Pulmonary Alveoli; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Thrombophilia; Urokinase-Type Plasminogen Activator

Goodpasture's, or anti-glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis and lung haemorrhage, and is caused by autoimmunity to the NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1). This study examines the development of crescentic nephritis and alveolar haemorrhage in a model of Goodpasture's disease, experimental autoimmune glomerulonephritis (EAG), induced in WKY rats by immunization with rat GBM in adjuvant. An increase in circulating anti-GBM antibodies and albuminuria was observed by week 2, which increased further by weeks 3 and 4, while a decrease in creatinine clearance was observed by week 2, which decreased further by weeks 3 and 4. The kidneys of animals with EAG showed linear deposits of IgG on the GBM and a transient glomerular infiltration by CD4+ T cells at week 2. By week 3 there were large deposits of fibrin in Bowman's space, and glomerular infiltration by CD8+ T cells and macrophages, accompanied by focal necrotizing glomerulonephritis with crescent formation. Ultrastructural studies showed glomerular endothelial cell swelling and epithelial cell foot process effacement at week 2. As the lesion progressed, capillary loops became occluded and the mesangium became expanded by mononuclear cells. By week 3 there was detachment of the endothelium from the GBM, and accumulation of fibrin beneath the disrupted endothelial cells and in Bowman's space. Occasional breaks were observed in the continuity of the basement membrane, and cytoplasmic projections from infiltrating mononuclear cells could be seen crossing the capillary wall between the lumen and the crescent. The lungs of animals with EAG showed patchy binding of IgG to the alveolar basement membrane (ABM) at week 2, and infiltration of the interstitium by CD8+ T cells and macrophages by weeks 3 and 4, accompanied by both interstitial and alveolar haemorrhage. Ultrastructural studies showed focal mononuclear cell infiltrates in alveolar walls at week 2. Occasional breaks were observed in the basement membrane and adjacent endothelium by weeks 3 and 4, together with accumulation of surfactant and erythrocytes within the alveolar spaces. This study defines for the first time the relationship between the immunological and pathological events during the evolution of EAG, and provides the basis for further work on the pathogenesis of Goodpasture's disease.

Topics: Animals; Anti-Glomerular Basement Membrane Disease; Antibodies; Autoantibodies; Autoimmune Diseases; Autoimmunity; Basement Membrane; Creatinine; Disease Models, Animal; Fibrin; Glomerulonephritis; Hemorrhage; Kidney Glomerulus; Lung Diseases; Male; Microscopy, Electron; Nephritis; Pulmonary Alveoli; Rats; Rats, Inbred WKY

Studies have shown that inhibition of TAFI by small peptides enhances pharmacological effects of tPA in animal models of thrombosis, suggesting that TAFI modulates the fibrinolytic system. In this study, we investigated the effect of activated human TAFI (TAFIa) on endogenous fibrinolysis in a rat model of intravascular fibrin deposition. (125)I-labeled fibrinogen was injected intravenously followed by a bolus injection of batroxobin, a thrombin-like enzyme. Batroxobin cleaved fibrinogen to form insoluble fibrin that was deposited in tissues, including the lungs. This was shown by a decrease of radioactivity in the blood as a result of consumption of (125)I-labeled fibrinogen and an elevation of radioactivity in the lungs 5 min following batrox-obin administration. Endogenous fibrinolysis was detected by a gradual increase in radioactivity in the blood and a decrease in radioactivity in the lungs at 30 min, an indication of radiolabeled fibrin degradation products (FDPs) being released into the circulation from the tissues. Intravenous administration of human TAFIa dose-dependently attenuated the later phase reduction of radioactivity in the lungs. When the dose of TAFIa was 218 micro g/kg, giving a peak plasma level of TAFIa 0.9 +/- 0.05 micro g/ml, the spontaneous fibrinolysis was completely prevented. These results provide direct evidence that an increase in circulating TAFIa impairs endogenous clot lysis in a rat model of fibrin deposition.

Topics: Animals; Batroxobin; Carboxypeptidase B2; Dose-Response Relationship, Drug; Fibrin; Fibrinogen; Fibrinolysis; Humans; Injections, Intravenous; Iodine Radioisotopes; Lung Diseases; Male; Rats; Thrombosis

In this study, we investigated if elevation of endogenous plasminogen activator inhibitor type 1 (PAI-1) by lipopolysaccharide (LPS) can retard thrombolysis in both a rat model of lung vasculature fibrin deposition and a platelet-rich thrombus model induced by endothelial injury. By 3 h following an intravenous bolus injection of 0.5 mg/kg LPS, the plasma PAI-1 level had increased to approximately 8 ng/ml. 125I-labeled fibrinogen was injected intravenously followed by an injection of batroxobin. Batroxobin converts fibrinogen into insoluble fibrin, which was then deposited in the lungs within 5 min, followed by spontaneous fibrinolysis that completely cleared fibrin deposition in the lungs by 30 min. In rats pre-treated with LPS, spontaneous fibrinolysis was significantly retarded. In the endothelial injury model, topical application of FeCl2 on the carotid artery induced an occlusive platelet-rich thrombus, which was not sensitive to endogenous thrombolysis. Exogenous tissue-type plasminogen activator (tPA) was required to recanalize the occlusive thrombus in a dose-dependent manner. Pre-treatment with LPS did not alter the dose-response curve of exogenous tPA-induced thrombolysis. These data indicate that batroxobin-induced lung vasculature fibrin deposition in rats, unlike the FeCl2 model, is sensitive to the impact of endogenous PAI-1 on fibrinolysis.

Topics: Animals; Batroxobin; Carotid Arteries; Carotid Artery Thrombosis; Ferrous Compounds; Fibrin; Lipopolysaccharides; Lung Diseases; Male; Plasminogen Activator Inhibitor 1; Rats; Rats, Sprague-Dawley; Tissue Plasminogen Activator

Lung fragments from 12 patients were collected immediately after death and studied by light and electron microscopy and by immunohistochemistry to describe the main morphologic and ultrastructural aspects of the lung and platelets in leptospirosis (Weil's syndrome), to search for the possibility of disseminated intravascular coagulation (DIC), and to assess the relationship between endothelial lesions and local platelet aggregation and the leptospiral antigen distribution, as well as its relationship with the intensity of the lesions. The immunohistochemical results for fibrin aggregates were positive in the lumen and/or on the vascular endothelium in nine cases and on the alveolar surface in seven cases, leading to the diagnosis of the adult respiratory distress syndrome in these seven cases. Test results for leptospiral antigen by immunohistochemistry were positive in eight cases with no direct relationship between antigen deposits in the pulmonary vascular endothelium and intensity of the lesions. The ultrastructural findings were uniform and constant. Capillary lesions were characterized by swelling of endothelial cells, an increase in pinocytotic vesicles, and giant dense bodies in the cytoplasm of these cells. No necrosis, rupture, nor exposed subendothelial collagen was observed outside the hemorrhagic areas, and the intercellular junctions were preserved. The lung involvement in severe human leptospirosis presents as hemorrhagic pneumopathy with septal capillary lesions that are the usual cause of death. The thrombocytopenia that was verified in 11 of 12 patients in our study seems to bear no relationship to DIC and seems to be determined by activation, adhesion, and aggregation of platelets to the stimulated vascular endothelium, with an amorphous electron-dense substance between the endothelial cells and the adherent platelets in places where the subendothelial collagen was not exposed.

Topics: Adult; Antigens, Bacterial; Blood Platelets; Capillaries; Cell Adhesion; Endothelium, Vascular; Female; Fibrin; Hemorrhage; Humans; Immunohistochemistry; Leptospira interrogans; Lung; Lung Diseases; Male; Microscopy, Electron; Middle Aged; Platelet Aggregation; Thrombocytopenia; Weil Disease

Bleomycin lung injury in mice leads to an acute alveolitis followed by a fibroproliferative response characterized by the accumulation of extracellular matrix. Because distinct regions of the fibrin(ogen) molecule have unique in vitro biological effects on cells, we quantified, localized, and biochemically characterized the molecular form of extravascular fibrin(ogen) in methoxyflurane anesthetized, bleomycin-injured mice. Bleomycin or saline (controls) was administered intratracheally, and lung tissue was harvested and analyzed at several times thereafter. Immunoreactive fibrin tissue content increased to a maximal 50-fold over controls in a temporal and spatial pattern paralleling that of alveolitis and maximal fibroproliferation. The generation of gamma-gamma-chain dimers and alpha-chain polymers, together with the loss of free alpha- and gamma-chains, indicates that the fibrin is predominantly covalently cross-linked. In fibroproliferative-phase lungs, the fibrin fibrils are branched and colocalize with those of collagen at the electron microscopic level. These observations strongly suggest that fibrin is a significant molecular effector of the in vivo fibroproliferative response after lung injury.

Topics: Animals; Bleomycin; Fibrin; Fibrinogen; Immunoenzyme Techniques; Lung Diseases; Mice; Mice, Inbred C57BL; Molecular Weight; Pulmonary Fibrosis

The purpose of this study was to determine whether a defect in hemostasis might be a factor in the etiology of exercise-induced pulmonary hemorrhage (EIPH). Hemostatic parameters were evaluated in 22 EIPH-positive and ten EIPH-negative racing horses while in a rested state. Nineteen EIPH-positive and ten EIPH-negative horses were further evaluated just before and immediately after a 15 min exercise period on a 260 m oval track. When EIPH-positive and EIPH-negative horses were compared at rest, there was no significant difference in any of the coagulation and fibrinolytic parameters studied. There was however, a significant difference in platelet function as assessed by aggregometry. The platelets from affected horses were significantly less responsive than those from nonaffected horses when exposed in vitro to the platelet agonists adenosine diphosphate, collagen and platelet activating factor. Exercise tended to increase the packed cell volume and factor VIII/von Willebrand factor and to decrease platelet aggregation responses to low concentrations of adenosine diphosphate. These effects of exercise however were quantitatively similar in both EIPH-positive and EIPH-negative horses. Reduced platelet function may therefore be a contributing factor in the bleeding characteristic of horses with EIPH.

Topics: Adenosine Diphosphate; Animals; Antithrombin III; Collagen; Factor VIII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hematocrit; Hemorrhage; Hemostasis; Horse Diseases; Horses; Lung Diseases; Partial Thromboplastin Time; Physical Exertion; Platelet Activating Factor; Platelet Aggregation; Platelet Count; Prothrombin Time; Thrombin Time; von Willebrand Factor

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.

Topics: Animals; Blood Coagulation; Cattle; Fibrin; Immunohistochemistry; Leukocytes; Lung Diseases; Macrophages; Male; Neutrophils; Pasteurella; Pasteurella Infections; Plasminogen Activators; Thromboplastin

Experimental pneumonia caused by Pasteurella haemolytica was induced in 2-week-old gnotobiotic (n = 4) and conventional (n = 6) calves by endobronchial inoculation into the right caudal lung lobe of 7.9 x 10(10) +/- 0.6 x 10(10) (mean +/- SD) colony-forming units of P haemolytica in the 6-hour log phase of growth. The calves were studied for 24 hours or less. Regression lines for the relationship between clinical index and time for the gnotobiotic group and conventional group of calves were compared, and the clinical index was found to be significantly (P less than or equal to 0.005) more rapid in the gnotobiotic group. There was also a significant difference in the preinoculation, absolute segmented neutrophil count (P less than or equal to 0.05), and in the total serum protein, albumin, and globulin values (P less than or equal to 0.05). Comparison of the preinoculation and post inoculation blood cell and blood chemical values revealed a significant increase (P less than or equal to 0.05) in the numbers of band neutrophils and fibrinogen in conventional calves, and a significant decrease (P less than or equal to 0.05) in the total WBC count in gnotobiotic calves. Necropsy of both groups of calves revealed a circular to oblong lesion that was congested, edematous, and firm, and which occupied 20% to 100% of the right caudal lung lobe and involved the remaining lung lobes to a more minor degree. When mean lesion scores of the 2 groups of calves were compared, no significant difference (P less than or equal to 0.05) was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cattle; Cattle Diseases; Female; Fibrin; Germ-Free Life; Lung Diseases; Male; Pasteurella; Pasteurellosis, Pneumonic; Pulmonary Edema; Time Factors

Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar-lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.

Topics: Adult; alpha-2-Antiplasmin; Antigens; Bronchoalveolar Lavage Fluid; Female; Fibrin; Fibronectins; Humans; Lung Diseases; Male; Middle Aged; Respiratory Distress Syndrome; Urokinase-Type Plasminogen Activator

Ten Pericarbon valve bioprostheses were examined after being implanted in tricuspid position in two different groups of animals: group I sheep with increased immunoglobulins, plasma levels, and eosinophilis count of more than 10%, due to parasitic infection, and group II sheep without any parasitic infection, i.e. with normal blood data. The explanted valve follow up was between 60-95 hours in both groups. Microscopic observation of group I valves revealed a massive blood cell (lymphocytes, eosinophilis and large mononuclear cells) infiltration especially around the natural pericardial blood vessels in the region of flexion and attachment. The epipericardial surface was covered by fibrin sheath, and immunofluorescence studies showed a strongly positive reaction for immunoglobulins (IgG and IgE) on leaflet surfaces and lamellar stratification into the fibrosa. Microcalcifications were detected around pericardial blood vessels in the same zones where infiltrated blood cells were found. In group II valves cell infiltration was absent with no signs of calcification and immunofluorescence was negative. Our data suggest that immunoglobulins adherence followed by blood cell infiltration may be one of the early causes of tissue leaflet degeneration and there is a parallel trend between plasma immunoglobulin levels and the early tissue alteration. Our data show that the experimental model for testing bioprostheses in sheep is influenced by the pre-immunological status and it is important to control it before surgery.

Topics: Animals; Bioprosthesis; Cell Movement; Fibrin; Fluorescent Antibody Technique; Heart Valve Prosthesis; Immunity; Immunoglobulins; Liver Diseases; Lung Diseases; Lymphocytes; Parasitic Diseases; Prosthesis Failure; Reference Values; Sheep

Extravascular, primarily intra-alveolar, fibrin deposition is a histologic hallmark of acute lung injury in humans and experimental animals, but the mechanisms leading to this finding are poorly understood. To determine whether local abnormalities in the fibrinolytic-procoagulant balance contribute to alveolar fibrin deposition in acute lung injury, we studied bronchoalveolar lavage (BAL) fluids of anesthetized sheep that received intravenous oleic acid. Prominent alveolar fibrin deposition was observed within 2 h after oleic acid-induced lung injury. Procoagulant and fibrinolytic activities were determined in BAL samples of anesthetized, mechanically ventilated sheep before and 2 h after intravenous oleic acid or saline. BAL procoagulant activity was found to be due mainly to tissue factor associated with Factor VII. In baseline BAL samples, we found relatively low levels of procoagulant activity and relatively high levels of fibrinolytic activity. After induction of oleic acid-induced lung injury, the procoagulant activity of BAL was markedly increased, whereas fibrinolytic activity was either depressed or undetectable. Antiplasmin activity was detectable in BAL of sheep after oleic acid-induced lung injury, which contributed at least in part to the depressed fibrinolytic activity observed. These perturbations occurred with the appearance of extensive alveolar fibrin deposition. In control sheep, BAL fibrinolytic activity was decreased, and antiplasmin activity increased modestly after 2 h of mechanical ventilation, but procoagulant activity was unchanged and alveolar fibrin was not observed. Procoagulant activity in lung lymph and plasma after lung injury did not differ from baseline values, and fibrinolytic activity was undetectable in lymph or plasma samples. These data indicate that increased procoagulant activity and concurrent disruption of the balance of coagulation and fibrinolysis establish local conditions that promote acute fibrin deposition in the alveoli of mechanically ventilated, oleic acid-injured sheep.

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation; Blood Proteins; Bronchoalveolar Lavage Fluid; Fibrin; Fibrinolysis; Hemodynamics; Lung; Lung Diseases; Lymph; Oleic Acid; Oleic Acids; Proteins; Pulmonary Alveoli; Sheep

Topics: Adolescent; Adult; Aged; Aprotinin; Calcium Chloride; Drug Combinations; Factor XIII; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Humans; Lung Diseases; Middle Aged; Thrombin; Tissue Adhesives

The authors describe a method of liquidation of a postresectional residual cavity by the introduction of the patient's autoblood with antibiotics. When using this method all the factors of the coagulating system of blood are involved in the formation of fibrin and the following formation of fibrothorax, which accelerates the formation of fibrothorax. The proposed method was used in 26 patients with residual pleural cavities after resection of the lungs and facilitated their liquidation and formation of fibrothorax.

Topics: Adult; Blood Transfusion, Autologous; Fibrin; Humans; Lung Diseases; Male; Middle Aged; Pleura; Pneumonectomy; Postoperative Care

The in vivo acquisition of coagulation plasma proteins on the surface of pulmonary macrophages was studied in guinea pigs breathing 95% oxygen. Fibrin/ogen and fibronectin appeared rapidly and concurrently on the surfaces of macrophages in the bronchoalveolar lavage fluid, which was judged by immunohistologic examination and flow cytometry. Pulmonary macrophages showed a parallel increase in the expression of a surface fibronectin receptor. Hyperoxic lung injury was accompanied by deposition of an extravascular pulmonary matrix of fibronectin and fibrin/ogen and depressed plasma levels of fibronectin. Binding to clot matrix proteins may lead to aggregation and retention of macrophages at sites of acute lung injury as well as alteration of cell function.

Topics: Animals; Female; Fibrin; Fibrinogen; Fibronectins; Fluorescein-5-isothiocyanate; Fluoresceins; Fluorescent Antibody Technique; Guinea Pigs; Lung; Lung Diseases; Macrophages; Male; Oxygen; Receptors, Fibronectin; Receptors, Immunologic; Therapeutic Irrigation; Thiocyanates

Seventy-five intimal arterial thickenings (from 58 subjects) related to pulmonary emboli were examined. Many showed residua derived from the emboli (fibrin, platelets, haemosiderin) and proliferation of elastica and smooth muscle cells. Features resembling those of atherosclerosis were the frequent presence of extracellular lipid and apolipoprotein-B containing lipoproteins (LpB) which corresponded closely in distribution; and (in about 40% of the thickenings) collections of fat-filled (foam) cells. Platelet antigens were often detected within foam cells in some cases, in company with LpB. The results indicate that at least some intimal thickenings originating from pulmonary emboli undergo transformation to atherosclerotic plaques. The role of pulmonary hypertension in the process was investigated. Mechanisms relevant to this transformation and to theories of atherogenesis are discussed.

Topics: Adolescent; Adult; Aged; Apolipoproteins B; Arteriosclerosis; Blood Platelets; Female; Fibrin; Fibrinogen; Foam Cells; Humans; Hypertension, Pulmonary; Lipid Metabolism; Lung Diseases; Male; Middle Aged; Pulmonary Embolism; Time Factors

A simple, effective and safe method is proposed to liquidate a persistent residual pleural cavity by a biological filling prepared ex tempore from a solution of fibrinogen with antibacterial drugs. The method was used in 24 patients after pleura empyema. The method of filling is described as well as the conditions for a successful use of the new means of liquidation of the residual pleural cavity and prevention of recurrent pleura empyemas.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bronchial Fistula; Combined Modality Therapy; Empyema; Fibrin; Fistula; Humans; Lung Diseases; Male; Pleural Diseases; Postoperative Complications; Prostheses and Implants; Skin Diseases

In 28 male Wistar rats a standardized lung incision was closed by running suture and in half of the animals by additional application of fibrin adhesive. The animals were sacrificed 30 minutes and 5 days postoperatively. A significantly higher tolerance to increased inflation pressure was found in the fibrin-treated group. Ten patients undergoing pulmonary resection had conventional closure of parenchymatous lesions with additional fibrin gluing. Under positive air way pressure ventilation the sealing effect proved to be better after application of fibrin adhesive to the sutured area.

Topics: Animals; Fibrin; Humans; Lung; Lung Diseases; Rats; Rats, Inbred Strains; Tissue Adhesions; Tissue Adhesives

The intratracheal injection into rabbits of low molecular weight C5-derived chemotactic fragments (C5fr), prepared from zymosan-activated serum, induced an acute pulmonary inflammation characterized by intraalveolar accumulation of neutrophils, erythrocytes, and edema fluid. In separate experiments, depletion of circulating pulmonary neutrophils and absorption of C5fr with immobilized antibody to homogenous human C5a prevented the observed inflammatory changes, indicating a requirement for these two elements in initiating this reaction. When examined by transmission and scanning electron microscopy, lungs of C5fr-injected rabbits revealed pulmonary neutrophils, often appearing partially degranulated, in alveolar, pulmonary capillary, and interstitial spaces. Alveolar spaces and, less often, the interstitial compartment contained fibrinoid deposits with leukocytes and erythrocytes enmeshed in the fibrin strands. Injury to the pulmonary vascular endothelium consisted of bleb formation in capillaries and endothelial basement membrane separation with subendothelial accumulation of inflammatory cells in venules. Type I, but not type II, epithelial cell damage included blebbing and epithelial cell basement membrane detachment. Endothelial and epithelial layer damage was always associated with pulmonary neutrophils continguous to the injured structures. These studies indicate the potential for alveolar epithelial and capillary injury in neutrophil-associated pulmonary inflammation resulting from intraalveolar accumulation of chemotactic substances.

Topics: Animals; Chemotaxis, Leukocyte; Complement C5; Edema; Female; Fibrin; Hemorrhage; Inflammation; Lung; Lung Diseases; Male; Microscopy, Electron, Scanning; Neutrophils; Rabbits

Immunofluorescence was performed on lung tissue obtained at necropsy from 18 newborn infants, including five with group B streptococcal (GBS) sepsis, seven with idiopathic respiratory distress syndrome (IRDS), and six control infants who died from other causes. Deposits of C3, IgG, and fibrin were found within hyaline membranes of infants who died with GBS sepsis or IRDS within 48 hours after birth. In some cases C4, factor B, and IgM were also observed. In five infants with IRDS who died more than five days after birth, immunofluorescent lung findings were less common and less intense. Hyaline membranes, attributed to mechanical ventilators and oxygen therapy in two infants who did not have GBS infection or IRDS, were negative for complement and immunoglobulins although fibrin was detected in one specimen. These data suggest that immunologic processes may contribute to the pathogenesis of certain types of acute lung injury, particularly in infants who die from GBS infection or IRDS during the early neonatal period.

Topics: Antigen-Antibody Complex; Complement C3; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Infant, Newborn; Infant, Newborn, Diseases; Lung; Lung Diseases; Respiratory Distress Syndrome, Newborn; Streptococcal Infections; Streptococcus agalactiae

To help differentiate pulmonary embolism from other lung diseases, we measured the degradation products of fibrinogen and fibrin and soluble fibrin complexes in normal control subjects and patients with pulmonary embolism, lung cancer, pneumonia, chronic obstructive pulmonary disease, tuberculosis, asthma, and several miscellaneous disorders. A separate group of patients, who were suspected of having pulmonary embolism but had negative pulmonary angiography, were also tested. Many nonthromboembolic lung diseases frequently were associated with positive fibrinogen/fibrin degradation products or soluble fibrin complexes, but those with high positivity rates for one test tended to have low rates for the other test. Both fibrinogen/fibrin degradation products and soluble fibrin complexes were positive in 55 per cent of patients with pulmonary embolism but only in 4 per cent with nonthromboembolic conditions (P less than 0.001), in 7 per cent of patients with negative pulmonary angiography (P less than 0.001), and in none of the normal subjects (P less than 0.001). Both tests were negative in only 3 per cent of patients with pulmonary embolism but in 35 per cent of nonthromboembolic diseases (P less than 0.005), 54 per cent of those with negative pulmonary angiography (P less than 0.001), and 79 per cent of normal control subjects (P less than 0.001). The combination of fibrinogen/fibrin degradation products and soluble fibrin complexes is more valuable than either test alone in the diagnostic separation of thromboembolic from nonthromboembolic pulmonary diseases.

Topics: Diagnosis, Differential; False Positive Reactions; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Lung Diseases; Pulmonary Artery; Pulmonary Embolism; Radiography

Fibrosing uremic pleuritis is a newly recognized late complication of uremia. Extreme incarceration of the lining and chest wall can occur with disabling restriction of pulmonary function. Decortication of the chest wall and the lung can be carried out safely with minimal bleeding and restoration of pulmonary function.

Topics: Adult; Female; Fibrin; Hemorrhage; Humans; Lung; Lung Diseases; Pleurisy; Radiography; Time Factors; Uremia; Wound Healing

Topics: Aprotinin; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysin; Humans; Lung Diseases; Pancreatitis; Shock

Topics: Adult; Basement Membrane; Biopsy; Collagen; Cytoplasm; Diagnosis, Differential; Epithelial Cells; Erythrocytes; Fibrin; Fluorescent Antibody Technique; Glycogen; Hemorrhage; Hemosiderin; Hemosiderosis; Humans; Leukocytes; Lung; Lung Diseases; Macrophages; Male; Microscopy, Electron; Pulmonary Alveoli; Pulmonary Edema

Topics: Animals; Blood Coagulation; Capillaries; Endothelium; Epithelial Cells; Extracorporeal Circulation; Fibrin; Humans; Lung; Lung Diseases; Lymphatic System; Microcirculation; Microscopy, Electron; Oxygen; Positive-Pressure Respiration; Pulmonary Circulation; Pulmonary Surfactants; Respiratory Insufficiency; Shock

Topics: Adult; Aged; Autoimmune Diseases; Biopsy, Needle; Bronchiectasis; Chronic Disease; Empyema; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Kidney; Kidney Diseases; Lung; Lung Diseases; Male; Microscopy, Electron; Middle Aged; Phagocytosis; Pleural Diseases; Pneumonia

Topics: Autopsy; Blister; Blood Coagulation Disorders; Duodenal Ulcer; Fibrin; Hemorrhage; Histocytochemistry; Humans; Infant; Kidney Glomerulus; Lung Diseases; Male; Mast Cells; Peptic Ulcer Hemorrhage; Shock, Hemorrhagic; Skin; Thrombosis; Urticaria Pigmentosa

Topics: Adolescent; Female; Femoral Fractures; Fibrin; Gastrointestinal Diseases; Humans; Lung Diseases; Pregnancy; Pregnancy Complications; Thrombosis; Wounds and Injuries

Topics: Acetylcysteine; Asthma; Bronchial Diseases; Cysteine; Cystic Fibrosis; Expectorants; Fibrin; Humans; Lung Diseases; Mucus; Sputum; Toxicology

Topics: Afibrinogenemia; Bone and Bones; Bone Diseases; Fibrin; Gastrointestinal Diseases; Humans; Hypertension; Hypertension, Portal; Lung Diseases; Male; Siblings

Topics: Fibrin; Fibrinolysin; Humans; Lung; Lung Diseases

Topics: Bronchi; Bronchial Neoplasms; Carcinoma, Bronchogenic; Fibrin; Humans; Lung Diseases; Neoplasms; Pneumonia

Topics: Fibrin; Fibrinolysis; Humans; Lung; Lung Diseases; Prothrombin

Topics: Fibrin; Humans; Lung; Lung Diseases; Pulmonary Edema; Sympathetic Nervous System