muramidase and Liver-Cirrhosis

Topics: Alcoholism; Aminopeptidases; Amylases; Aspartate Aminotransferases; Cholinesterases; Creatine Kinase; Cystic Fibrosis; Enzyme Activation; Enzymes; Female; gamma-Glutamyltransferase; Half-Life; Humans; Isoenzymes; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Muramidase; Myocardial Infarction; Pepsinogens; Phenobarbital; Porphyrias; Pregnancy

The risk of mortality from pneumonia caused by Streptococcus pneumoniae is increased in patients with cirrhosis. However, the specific pneumococcal virulence factors and host immune defects responsible for this finding have not been clearly established. This study used a cirrhotic rat model of pneumococcal pneumonia to identify defect(s) in innate pulmonary defenses in the cirrhotic host and to determine the impact of the pneumococcal toxin pneumolysin on these defenses in the setting of severe cirrhosis.. No cirrhosis-associated defects in mucociliary clearance of pneumococci were found in these studies, but early intrapulmonary killing of the organisms before the arrival of neutrophils was significantly impaired. This defect was exacerbated by pneumolysin production in cirrhotic but not in control rats. Neutrophil-mediated killing of a particularly virulent type 3 pneumococcal strain also was significantly diminished within the lungs of cirrhotic rats with ascites. Levels of lysozyme and complement component C3 were both significantly reduced in bronchoalveolar lavage fluid from cirrhotic rats. Finally, complement deposition was reduced on the surface of pneumococci recovered from the lungs of cirrhotic rats in comparison to organisms recovered from the lungs of control animals.. Increased mortality from pneumococcal pneumonia in this cirrhotic host is related to defects in both early pre-neutrophil- and later neutrophil-mediated pulmonary killing of the organisms. The fact that pneumolysin production impaired pre-neutrophil-mediated pneumococcal killing in cirrhotic but not control rats suggests that pneumolysin may be particularly detrimental to this defense mechanism in the severely cirrhotic host. The decrease in neutrophil-mediated killing of pneumococci within the lungs of the cirrhotic host is related to insufficient deposition of host proteins such as complement C3 on their surfaces. Pneumolysin likely plays a role in complement consumption within the lungs. Our studies, however, were unable to determine whether pneumolysin more negatively impacted this defense mechanism in cirrhotic than in control rats. These findings contribute to our understanding of the defects in innate pulmonary defenses that lead to increased mortality from pneumococcal pneumonia in the severely cirrhotic host. They also suggest that pneumolysin may be a particularly potent pneumococcal virulence factor in the setting of cirrhosis.

Topics: Animals; Bacterial Proteins; Bronchoalveolar Lavage Fluid; Cell Wall; Complement C3; Immunity, Innate; Liver Cirrhosis; Lung; Male; Microbial Viability; Muramidase; Pneumonia, Pneumococcal; Rats; Rats, Sprague-Dawley; Streptococcus pneumoniae; Streptolysins

Some peptide growth factors produced by macrophages play a role in fibrosis following tissue injury, through the induction of myofibroblasts. In the present study, the appearance of macrophages and myofibroblast development in hepatic and renal fibrosis was determined by immunohistochemical analysis of tissue from 15 dogs. The hepatic and renal fibrosis was classified as grade I, II or III, depending on the extent (percentage) of fibrotic areas per unit area measured by morphometry with Azan-stained sections. The presence of alpha-smooth muscle actin-immunolabelled myofibroblasts was directly related to advancing grade of both hepatic and renal fibrosis. Lysozyme-immunolabelled macrophages also increased in number with increasing grade of hepatic and renal fibrosis. These findings indicate that myofibroblasts and lysozyme-positive macrophages may contribute to progressive fibrosis in canine liver and kidney disease. Interestingly, the number of macrophages recognized by AM-3K, a newly generated monoclonal antibody capable of labelling exuded macrophages and resident tissue macrophages in dogs, fell significantly in grades II and III of renal fibrosis. By contrast, in hepatic fibrosis there were no marked differences in the number of AM-3K-positive macrophages between grades. These findings suggest that there are functional differences between lysozyme- and AM-3K-positive macrophages.

Topics: Actins; Animals; Antibodies, Monoclonal; Cell Count; Dogs; Female; Fibroblasts; Fibrosis; Immunohistochemistry; Liver Cirrhosis; Macrophages; Male; Muramidase; Muscle, Smooth; Nephritis, Interstitial

Some urinary enzymes (NAG, AAP, lysozyme) considered to be sufficiently sensitive and reliable markers of renal damage were controlled in 20 patients with cirrhosis of the liver and in 20 healthy control subjects. The results, stated as mean +/- SD, showed a statistically very significant increase (p < 0.01) of NAG and lysozyme in cirrhotics. Furthermore, this increase could be at least in part related with the seriousness of clinical condition. On the basis of these results, we think the urinary dosage of NAG and lysozyme is, in the subjects with liver cirrhosis, a bloodless method to show an early renal damage.

Topics: Acetylglucosaminidase; Adult; Aged; Aged, 80 and over; Aminopeptidases; Ascites; Butyrylcholinesterase; CD13 Antigens; Clinical Enzyme Tests; Diabetes Mellitus; Female; Humans; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Muramidase; Time Factors

Lysozyme is a bacteriocidal enzyme which is a major stable secretory product of mononuclear phagocytes, including hepatic sinusoidal macrophages (HSM), and serves as a good marker for these cells. Patients with alcoholic liver disease (ALD) have decreased HSM function which is reflected in reduced clearance of microorganisms and endotoxin derived from the gut. The HSM population in 54 liver biopsies from patients with ALD was studied using immunoperoxidase staining of lysozyme and was compared with 15 histologically normal controls. In both groups lysozyme positive HSM were more numerous in periportal than perivenous parenchyma. In each zone there were significantly fewer positive HSM in cases of ALD than in controls, in alcoholic hepatitis than in ALD without hepatitis, and in cirrhosis than in ALD without cirrhosis. These findings suggest a decreased population of functionally active HSM in ALD which correlates with severity of liver damage. This might be due to decreased lysozyme content of the entire HSM population or to the existence of two populations, one positive and one negative for lysozyme. The observed decrease in HSM function explains many of the phenomena observed in ALD.

Topics: Hepatitis, Alcoholic; Humans; Immunoenzyme Techniques; Liver; Liver Cirrhosis; Liver Diseases, Alcoholic; Macrophages; Muramidase

Topics: Chronic Disease; Hepatitis; Humans; Liver Cirrhosis; Middle Aged; Muramidase

Plasma lysozyme levels have been reported to reflect the functional status of the reticuloendothelial system (RES). We measured plasma lysozyme levels in 22 patients with acute hepatitis and 21 patients with cirrhosis and a mesocaval shunt. In 17 of these patients RES function was assessed by measuring the disappearance rate (t/2) of radio-labelled sulphur colloid. In acute hepatitis plasma lysozyme levels and colloid t/2 were significantly lower than in health controls and cirrhotics. In the acute hepatitis patients, the plasma lysozyme levels rose significantly two weeks after admission as the hepatitis improved. The colloid t/2 of the 17 patients with liver disease was significantly correlated with the plasma lysozyme level (r = +0.66, p = 0.005). These results suggest that in human liver disease, in comparison with animal experiments, plasma lysozyme is dependent on RES functional status in the sense that a more active RES will result in a lower lysozyme level.

Topics: Acute Disease; Adult; Aged; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Middle Aged; Mononuclear Phagocyte System; Muramidase; Sulfur; Technetium; Technetium Tc 99m Sulfur Colloid

Topics: alpha-Glucosidases; beta 2-Microglobulin; Beta-Globulins; Diuresis; Humans; Kidney Diseases; Liver Cirrhosis; Muramidase

The serum bactericidal activity (SBA) of cirrhotic patients was compared with that of normal individuals using the release of (51)Cr from radiolabeled Escherichia coli as the assay method. 80% (22/27) of patients were found to have deficient SBA against at least one of three smooth, serum-sensitive test strains of E. coli. Cirrhotic patients were found to have normal levels of serum lysozyme. Although some patients were mildly hypocomplementemic, this abnormality did not correlate with the presence of a bactericidal defect. Bactericidal antibody in normal and cirrhotics' sera was limited to the immunoglobulin (Ig)M class. Purified IgM from patients with deficient SBA against E. coli 0111 had lower concentrations of bactericidal antibody for that E. coli than did IgM from normal sera; the calculated bactericidal activity of total serum IgM was also lower. The bactericidal defect in cirrhotic serum could be completely corrected by either human antiserum to the homologous strain of E. coli or by purified, normal human IgM. However, because higher concentrations of IgM were required to restore normal SBA to a cirrhotic's serum than to agammaglobulinemic serum, there may be an inhibitor of bactericidal antibody in addition to a deficiency of bactericidal IgM antibody to E. coli in the serum of patients with cirrhosis. The bactericidal activity of the alternative complement pathway was also assessed. Sera from cirrhotic patients had no deficit in SBA attributable to the alternative complement pathway. In fact, in some, the activity of the alternative complement pathway was supernormal, compensating in part for the deficit in IgM-mediated SBA.

Topics: Antibodies, Bacterial; Blood Bactericidal Activity; Chromium Radioisotopes; Complement C3; Complement C4; Complement Factor B; Escherichia coli; Humans; Immunoglobulin G; Immunoglobulin M; Liver Cirrhosis; Muramidase

Measurements of urinary lysozyme were used to evaluate renal tubular integrity in 34 patients with cirrhosis or fulminant hepatic failure who had developed renal impairment. In 18 of the patients the lysozyme values were normal but in the remaining 16 were increased, supporting previous concepts that renal failure complicating hepatocellular disease may occur both without and with tubular necrosis. The lysozyme values were inversely related to the creatinine clearance, suggesting that the development of tubular necrosis may be determined by the level of renal perfusion. The validity of simpler laboratory tests often used to assess renal tubular integrity--namely, the urine sodium concentration, the urine:plasma osmolality ratio, and casts in the urine sediment--was evaluated by comparison with the lysozyme measurements. The urine sodium concentration was of most value and the findings in the sediment were of no value at all.

Topics: Acute Kidney Injury; Humans; Kidney Tubular Necrosis, Acute; Kidney Tubules; Liver Cirrhosis; Liver Diseases; Muramidase; Sodium

Topics: Adult; Alcoholism; Ascitic Fluid; Bacteroides fragilis; Complement C3; Complement C4; Enterococcus faecalis; Escherichia coli; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Klebsiella pneumoniae; Liver Cirrhosis; Male; Middle Aged; Muramidase; Peritonitis; Streptococcus pneumoniae

The effect of properdin, lysozyme and complementary activity of the blood serum on the degree of immune alteration of leukocytes was revealed on the clinico-experimental material. In the leukocytolysis a neutrophil apparently serves as a mechanical substrate. It is likely that the cytophilic organic antibodies conditioned the indirect variety of leukocytolysis.

Topics: Adult; Aged; Animals; Complement System Proteins; Female; Humans; Leukocytes; Liver Cirrhosis; Male; Middle Aged; Muramidase; Neutrophils; Properdin; Rabbits

The study of some factors of nonspecific immunity in 85 patients with cirrhosis and in 9 patients with primary cancer of the liver revealed a decrease of all factors of nonspecific immunity under consideration, while in primary cancer of the liver--selective and more sharp fall of properdin level. The complement, as compared with the control, was not changed, whereas lysozyme was statistically reliably higher than in healthy persons.

Topics: Adult; Aged; Complement System Proteins; Diagnosis, Differential; Humans; Immunity; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Muramidase; Properdin

A prospective study was conducted to define the content, significance, and source of lysozyme present in the pleural fluid in human diseases. The pleural fluid lysozyme activity is similar in various malignant and nonmalignant transudates and exudates, and is of limited diagnostic value. The pleural fluid activity correlated well with that of paired serum samples but it had poor correlation with the disease state, the pleural fluid granulocyte counts, and total white blood cell counts. The data suggest that the pleural fluid lysozyme may be derived primarily from the blood and that it is not the product of inflammatory or neoplastic cells in the fluid itself.

Topics: Carcinoma; Female; Granulocytes; Heart Failure; Humans; Leukemia; Liver Cirrhosis; Lung Neoplasms; Lymphoma; Male; Muramidase; Pleural Effusion

Topics: Adult; Complement System Proteins; Evaluation Studies as Topic; Humans; Liver Cirrhosis; Middle Aged; Muramidase; Properdin

Topics: Humans; Immunodiffusion; Liver Cirrhosis; Micrococcus; Muramidase; Prognosis

Topics: Autoantibodies; Bone Marrow; Complement System Proteins; Fatty Liver; Hepatitis; Humans; Immunoglobulins; Liver; Liver Cirrhosis; Monocytes; Muramidase; Skin

Topics: Bile; Complement System Proteins; Duodenum; gamma-Globulins; Humans; Immunodiffusion; Intestinal Secretions; Leukocytes; Liver Cirrhosis; Muramidase; Opsonin Proteins; Pancreatic Juice; Pancreatitis; Phagocytosis

Topics: Adolescent; Adult; Bone Marrow Cells; Complement System Proteins; Female; Humans; Immunity, Active; Liver Cirrhosis; Male; Middle Aged; Muramidase; Plasma Cells