muramidase and Pulmonary-Fibrosis

Pulmonary fibrosis is a progressive scarring disease of the lung. It has been suggested that fibrosis is an inflammatory process, and cytokines such as tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta have been shown to play key roles in the pathogenesis of fibrotic lung disease. However, the source of these cytokines remains in question and there is controversy over the role that infiltrating inflammatory cells play in fibrosis. T cells could play a key role by releasing cytokines upon engaging autoantigens revealed as a result of necrosis or apoptosis following epithelial injury. Some studies have shown that disrupting T-cell function leads to more severe disease, whereas others have shown that T-cell deficiency protects against fibrotic injury. To investigate whether specific antigen engagement by T cells is required for the development of fibrosis, bleomycin was instilled into the lungs of mice expressing a transgenic T-cell receptor beta (TCRbeta) gene. Expression of the TCRbeta transgene prevents effective recognition of antigens other than a single epitope of hen egg lysozyme. These mice therefore have defective antigen-specific responses but a normal representation of mature T-cell subsets. If antigen-specific T-cell engagement is required for the development of lung fibrosis, bleomycin-induced fibrosis should be reduced in the TCRbeta transgenic mice. In fact, there is no difference in the inflammatory or fibrotic response to bleomycin between TCRbeta transgenic and control mice. Thus, if T cells are required for fibrogenesis, it must involve an antigen-independent mechanism.

Topics: Amino Acid Sequence; Animals; Antigens; Bleomycin; Chickens; Genes, T-Cell Receptor beta; Lung; Lung Injury; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Muramidase; Pulmonary Fibrosis; T-Lymphocytes

Lysozyme is increased in inflammatory reactions and is a component of the extracellular matrix, but its possible role in lung diseases such as emphysema and interstitial fibrosis has not been investigated.. To characterise differences in lysozyme content among normal, emphysematous, and fibrotic human lungs, tissue sections obtained from necropsy specimens were immunostained with rabbit polyclonal anti-human lysozyme antibody using the labelled streptavidin-biotin peroxidase method. The immunostained sections were evaluated semi-quantitatively (grading the degree of immunostaining on a scale of 0-4). To determine if degradation of the extracellular matrix affects lysozyme binding, hyaluronidase-treated normal lung tissues were incubated with egg white lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg white lysozyme, and evaluated for degree of staining.. Lysozyme immunostaining was significantly increased in lungs with pulmonary emphysema compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p < 0.05) and was preferentially associated with interstitial elastic fibres. Hyaluronidase-treated lung tissues incubated with lysozyme showed increased immunostaining for this protein compared with untreated controls (1.9 versus 1.2; p < 0.05).. The results suggest that damage to elastic fibres and/or the surrounding extracellular matrix increases lysozyme binding. It is hypothesised that attachment of lysozyme to elastic fibres may interfere with their repair and possibly enhance the progression of pulmonary emphysema.

Topics: Elastic Tissue; Extracellular Matrix; Humans; Hyaluronoglucosaminidase; Immunoenzyme Techniques; Lung; Muramidase; Pulmonary Emphysema; Pulmonary Fibrosis; Statistics, Nonparametric

Own experiences in practical application of immunohistochemistry are demonstrated in cases of lung fibrosis, sarcoidosis, tuberculosis and allergic vasculitis. Methods for demonstration of immunoglobulins (IgG, IgE) are useful in diagnosis of allergic vasculitis (IgG) and allergic alveolitis (IgE). Lysozyme is an important morphological parameter for the estimation of the activity of sarcoidosis. First results of application of antisera against mycobacteria and Kveim antigen are discussed in respect to more precise differential diagnosis of granulomatous lung diseases (sarcoidosis, tuberculosis).

Topics: Alveolitis, Extrinsic Allergic; Antigens, Bacterial; Humans; Immunoglobulins; Immunohistochemistry; Lung; Lung Diseases; Muramidase; Mycobacterium; Pulmonary Fibrosis; Sarcoidosis; Tuberculosis, Pulmonary; Vasculitis

Topics: Antigen-Antibody Complex; Humans; Lung Diseases; Muramidase; Peptidyl-Dipeptidase A; Pulmonary Fibrosis; Sarcoidosis

Serum angiotensin-converting enzyme (ACE) activity was studied in healthy controls, in 57 untreated sarcoidosis patients, and in 164 patients with other chest or lymph node diseases. The serum ACE activity of healthy persons was independent of sex, intake of meals, and smoking habits. There were no diurnal variations. Healthy children had a significantly higher ACE mean value than adults, whose ACE activity was not affected by age. The sarcoidosis patients had the highest ACE mean values, but those of patients with silicosis and asbestosis were also significantly elevated. Pulmonary cancer patients had decreased serum ACE activity, which was probably due to antimitotic treatment. Serum lysozyme (LZM) concentrations did not correlate with normal ACE activity, but the correlation between elevated ACE and LZM was significant in sarcoidosis and silicosis, and the trend was clearly the same for asbestosis. This indicates separate sources for these enzymes when ACE activity is normal, and a common source, i.e. macrophages, when ACE activity is increased. ACE production in certain diseases involving macrophages may be due to the bradykinin inhibiting effect of this enzyme.

Topics: Adolescent; Adult; Alveolitis, Extrinsic Allergic; Asbestosis; Bronchitis; Female; Hodgkin Disease; Humans; Lung Diseases; Lung Neoplasms; Lymphatic Diseases; Lymphoma; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Pneumonia; Pulmonary Fibrosis; Sarcoidosis; Silicosis; Thoracic Neoplasms; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary