fibrin and Tuberculosis--Pulmonary

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.

Topics: Animals; Bacteremia; Blood Coagulation; Cell Differentiation; Female; Fibrin; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Macrophages; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; Pneumonia; Thromboplastin; Tuberculoma; Tuberculosis, Pulmonary

Mycobacterium tuberculosis, the causative agent of tuberculosis, drives the formation of granulomas, structures in which both immune cells and the bacterial pathogen cohabit. The most abundant cells in granulomas are macrophages, which contribute as both cells with bactericidal activity and as targets for M. tuberculosis infection and proliferation during the entire course of infection. The mechanisms and factors involved in the regulation and control of macrophage microenvironment-specific polarization and plasticity are not well understood, as some granulomas are able to control bacteria growth and others fail to do so, permitting bacterial spread. In this issue of the European Journal of Immunology, Venkatasubramanian et al. [Eur. J. Immunol. 2016. 46: 464-479] show that mice lacking the tissue factor gene in myeloid cells have augmented M. tuberculosis growth and increased inflammation in the lungs. This suggests that tissue factor, an initiator of coagulation, is important for the generation of fibrin, which supports granuloma formation. This article demonstrates for the first time the involvement of tissue factor in inducing effective immunity against M. tuberculosis, and sheds new lights on the complex interplay between host inflammatory response, the coagulation system, and the control of M. tuberculosis infection.

Topics: Animals; Bacteremia; Blood Coagulation; Cell Differentiation; Fibrin; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Macrophages; Mice; Mice, Knockout; Mycobacterium tuberculosis; Pneumonia; Thromboplastin; Tuberculoma; Tuberculosis, Pulmonary

Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB.

Topics: Animals; Collagen; Disease Models, Animal; Down-Regulation; Etanercept; Fibrin; Granuloma; Inflammation; Lung; Mycobacterium tuberculosis; Rabbits; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Up-Regulation

The effect of trental on hemostasys system depending on the degree of heart failure was studied in patients with fibrocavernous pulmonary tuberculosis complicated by chronic pulmonary heart disease. Established the desirability of placing trental in the treatment regimen of patients with fibrocavernous pulmonary tuberculosis and compensated CPHD in order to correct violations of the microcirculation and prevention of circulatory decompensation.

Topics: Antithrombins; Blood Coagulation; Cell Aggregation; Fibrin; Fibrinogen; Humans; Lung; Pentoxifylline; Platelet Count; Pulmonary Heart Disease; Tuberculosis, Pulmonary

One hundred and twenty-four patients with different forms of active pulmonary tuberculosis were examined. The fibrinolytic system was assessed from the time of plasma fibrin clot lysis, plasminogen (PG) concentrations, and alpha2-antiplasmin (alpha2-AP) activity. The findings were compared with the recordings of a coagulogram, the concentration ofintravascular coagulation (IVC) markers--soluble fibrinmonomer complexes (SFMC) and D-dimers (DD), as well as with systemic inflammation indices (C-reactive protein and haptoglobin). The patients with pulmonary tuberculosis were found to have a hypercoagulation shift in the hemostatic system, which was accompanied by IVC events and quantitatively associated with the degree of systemic inflammation. This was followed by the moderately elevated PG concentrations in a third of patients and enhanced alpha2-AP activity in two thirds. The prevailing alpha2-AP rise resulted in delayed forming fibrin lysis. When influenced by a number of competitive factors, the values of PG and alpha2-AP directly correlated only with fibrinogen levels (directly). The concentration of DD directly correlated with the markers of systemic inflammation and SFMC, showed no correlations with the indices of the fibrinolytic and hemostatic systems. No correlations between PG, alpha2-AP, and DD suggests that in addition to secretion of corresponding factors, processes of their uptake play a large role in the formation of the functional status of the fibrinolytic system.

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; Blood Coagulation Tests; C-Reactive Protein; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen; Tuberculosis, Pulmonary

Topics: Fibrin; Fibrinogen; Humans; Lung Neoplasms; Pleural Effusion; Tuberculosis, Pulmonary

Topics: Adult; Female; Fibrin; Humans; Pleural Effusion; Postoperative Complications; Radiography; Thoracic Surgery; Tuberculosis, Pulmonary

Two patients who developed reversible renal failure during intermittent rifampicin therapy are described. Both had febrile reactions to rifampicin. The first was also found to have uraemia associated with swelling of the glomerular endothelial cells. The second developed tubular necrosis unassociated with haemolysis or shock. The pathogenesis of the renal lesion in these two patients, as revealed by light microscopy, immunofluorescence studies and electron microscopy, is discussed.

Topics: Acute Kidney Injury; Adult; Antibodies; Endothelium; Ethambutol; Fever; Fibrin; Humans; Immune Complex Diseases; Ischemia; Kidney Glomerulus; Kidney Tubules; Male; Necrosis; Rifampin; Tuberculosis, Pulmonary; Uremia

Topics: Aged; Biopsy; Collagen; Diagnosis, Differential; Fibrin; Humans; Lung; Male; Pulmonary Alveoli; Pulmonary Fibrosis; Radiography; Spondylitis, Ankylosing; Tuberculosis, Pulmonary

Topics: Adult; Aged; Asbestosis; Calcinosis; Diagnosis, Differential; Female; Fibrin; Humans; Male; Mesothelioma; Middle Aged; Pleural Diseases; Pleural Neoplasms; Pneumothorax, Artificial; Radiography; Tissue Adhesions; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Antitubercular Agents; Drug Therapy; Fibrin; Focal Infection; Lymphocytes; Tuberculosis; Tuberculosis, Pulmonary

In a study of caseous pulmonary nodules, it was found possible to identify the cellular and connective tissue background of the caseous material. In the absence of liquefaction, the connective tissues were found to retain their reaction to special stains indefinitely, and fibrin could be identified for periods up to one year after the onset of caseation. This allowed recognition of the part of lung involved and of pathological changes which had preceded caseation. Identification of the site of the suppurative "focus" in the respiratory bronchiole was important because bacilli could be found there most readily. Though lesions often outlined the acinus with clarity, the only value of the term "acinar" was to define the limits of one particular lesion.

Topics: Coloring Agents; Connective Tissue; Elastin; Fibrin; Granulation Tissue; Humans; Lung; Pathology; Staining and Labeling; Terminology as Topic; Tuberculosis; Tuberculosis, Pulmonary

Topics: Animals; Collapse Therapy; Fibrin; Lung; Porifera; Tuberculosis; Tuberculosis, Pulmonary

Topics: Fibrin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Fibrin; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary