Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E1 (PGE1) has recently been used clinically as a purported modulator of activated neutrophils in certain forms of the adult respiratory distress syndrome (ARDS). We now report that PGE1 does not have a uniform inhibitory effect upon human neutrophil functions in vitro. Cells were first pretreated with PGE1 followed by incubation with either N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol myristate acetate (PMA), or C5a. Lysosomal enzyme release (myeloperoxidase, lysozyme), superoxide anion generation, and chemotaxis were then quantitated. PGE1 alone lacked any appreciable effect on these neutrophil functions. However, neutrophils pretreated with PGE1 (50 to 100 microM) followed by stimulation with FMLP (50 nM) showed as much as 40% inhibition of lysosomal enzyme release compared with control values (p less than 0.0005). In contrast, 0.1 nM to 1 microM PGE1 enhanced FMLP-stimulated enzyme release as much as 50% above baseline control values (p less than 0.05). Preincubation with 0.1 nM PGE1 followed by stimulation with variable doses of FMLP also resulted in enhancement of lysosomal enzyme release by as much as 187 +/- 3% of control values. The enhancing but not inhibitory effects of PGE1 were reversible with serial washing of the neutrophil preparations. Enhancement of enzyme release was not observed when either PMA or C5a was used as a stimulus after PGE1 pretreatment. However, cells pretreated with PGE1 (50 to 100 microM) and subsequently stimulated with C5a showed as much as 40% inhibition of lysosomal enzyme release. Preincubation of neutrophils with PGE1 (1 microM) resulted in a slight (15%) enhancement of chemotaxis to FMLP, but it had no significant effect on C5a-induced chemotaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Concentration-dependent regulatory effects of prostaglandin E1 on human neutrophil function in vitro. 165 39

Inflammatory cytokines, including interleukin-1 and tumor necrosis factor, are produced by monocytes and macrophages in response to microorganisms and microbial products such as endotoxins. The cytokines stimulate neutrophil adherence, degranulation, and superoxide production but inhibit neutrophil migration. We studied the modulation of cytokine-induced neutrophil activation by pentoxifylline and its principle metabolites. Lipopolysaccharide-stimulated mononuclear-leukocyte-conditioned medium containing inflammatory cytokines, purified human interleukin-1, or recombinant human tumor necrosis factor increased neutrophil adherence to nylon fiber, primed neutrophils for increased superoxide production in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), increased neutrophil lysozyme release stimulated by FMLP, and decreased directed migration of neutrophils to FMLP. Pentoxifylline and its principle metabolites at or near therapeutically achievable levels were able to counteract these effects. Pentoxifylline inhibited the increase in free intracellular calcium in polymorphonuclear leukocytes stimulated by FMLP and increased binding of FMLP to neutrophils at 37 degrees C but not at 4 degrees C. By blocking the inflammatory action of interleukin-1 and tumor necrosis factor on neutrophils, pentoxifylline may diminish the tissue damage caused by neutrophils in such conditions as septic shock, adult respiratory distress syndrome, cardiopulmonary bypass lung damage, and myocardial reperfusion injury.
 ...
PMID:Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. 283 24

Hydrogen peroxide levels were measured in the breath condensate of 43 patients receiving mechanical ventilation. In 16 patients the mean breath condensate peroxide level was 1.68 +/- 0.35 mumol/l on the day they met diagnostic criteria for adult respiratory distress syndrome (ARDS). The peak breath condensate peroxide level in the 27 patients in whom ARDS did not develop was significantly lower (0.34 +/- 0.08 mumol/l). Plasma lysozyme, a measure of in-vivo neutrophil turnover, was significantly higher in ARDS than in non-ARDS patients (9.2 +/- 2.2 U/ml v 3.4 +/- 1.1 U/ml). These findings support the hypothesis that neutrophil activation and oxidant production are involved in the pathogenesis of ARDS.
 ...
PMID:Oxidant activity in expired breath of patients with adult respiratory distress syndrome. 286 61

A 14 kDa basic protein isolated from rat lung lavage was demonstrated to be lysozyme by its amino acid sequence analysis. An antiserum to rat lysozyme stained type II pneumocytes and alveolar macrophages. In rat lungs, no staining of the airway cells was noted. Lysozyme was detectable in type II pneumocytes by immunocytochemistry and by a quantitative immunoassay of lung homogenates of fetal lungs at Day 20 of gestation. An increase in the lysozyme content of the lung with increasing gestational and postnatal age of the rat was noted. In adult animals, lysozyme accounts for about 169.0 micrograms/g of wet lung weight and 0.3% of the soluble proteins in lung homogenate. Lysozyme constitutes about 6.6% of the total soluble proteins in rat lung lavage. Metabolic labeling and immunoprecipitation were used to demonstrate that rat type II pneumocytes synthesize and secrete lysozyme in vitro. However, in human lungs, lysozyme was identified in serous submucosal glands but not in alveolar type II pneumocytes. The results demonstrate differential distribution of a secretory protein in rodent and human lungs and indicate that in the rat lysozyme could be used as an immunohistologic marker for type II pneumocytes and as an indicator of secretory activity and maturation of type II pneumocytes.
 ...
PMID:Pulmonary lysozyme--a secretory protein of type II pneumocytes in the rat. 320 83

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.
 ...
PMID:Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. 400 15

Although prolonged Gram-negative sepsis with high permeability alveolar edema, a well documented cause of adult respiratory distress syndrome, has been shown to result in surfactant alterations, the effects of acute endotoxemia on the lung surfactant system are largely unknown. In this study, lethal endotoxemia (> 80% mortality at 24 h) resulting in severe, rapid leukopenia with progressive thrombocytopenia was achieved through intraperitoneal injection of adult Fischer 344 rats with 3.5 mg of Escherichia coli endotoxin/kg. After assessment of pulmonary mechanics under general anesthesia, endotoxin-injected rats and appropriate controls were killed at 4, 8, and 12 h for morphological and biochemical analyses. Morphometric estimation of surfactant membrane subtypes in bronchoalveolar lavage fluid revealed prominent alterations including significant decrease (45%) in tubular myelin 12 h post-endotoxin, with a threefold increase in lamellar body-like forms at 8 and 12 h. Acute endotoxicosis resulted in decrease of total dynamic compliance, whereas pulmonary resistance remained unchanged. These changes were associated with margination of polymorphonuclear leukocytes in lung microcirculation, multifocal septal edema, and decrease in lamellar body lysozyme specific activity at 12 h. Alveolar edema, as determined by measurement of total protein in cell-free bronchoalveolar lavage fluid, was absent in both controls and endotoxin-injected rats. The results indicate that bloodborne lung injury induced by lethal endotoxicosis initiates acute perturbation of secreted surfactant membranes with pulmonary dysfunction in the absence of high protein alveolar edema.
 ...
PMID:Depletion of surfactant tubular myelin with pulmonary dysfunction in a rat model for acute endotoxemia. 774 73

Lung surfactant is subject to oxidant injury from inhaled pollutants and free radicals generated by activated leukocytes in various disease states. Both lipid and protein components of surfactant can be altered by oxygen radicals. Changes were investigated in the lung surfactant system using a rat model with ozone injury to simulate adult respiratory distress syndrome, in which surfactant activity is thought to be inadequate. A significant decrease in dynamic lung compliance was correlated with the accumulation of protein in the alveolar lavage fluid. The amount of dipalmitoylphosphatidylcholine, the most abundant phospholipid in surfactant, increased two-fold indicating that the acute changes in lung function were related to the inactivation of surfactant by edema fluid and not to a quantitative lack of surfactant phospholipids. The amount of surfactant stored in lamellar bodies of the alveolar type II cells also increased and was abnormal in composition. The amount of cholesterol and albumin increased following ozone stress, suggesting that an altered uptake and incorporation of alveolar components into the lamellar bodies may be an important process in oxidant-induced lung injury. In contrast, lysozyme, an abundant protein in the alveolar fluid and lamellar bodies, rapidly decreased in concentration in the intracellular surfactant. Using an in vitro system we found that lysozyme is very sensitive to ozone injury and may function as a "sacrificial" antioxidant in the alveolar lining fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Oxidant-induced alterations of lung surfactant system. 813 36

Phagocytic cells, such as polymorphonuclear neutrophils, monocytes, and macrophages, are essential for defense against infection caused by a variety of microorganisms. The mechanisms used by these cells to destroy microbes comprise a potent oxidative armamentarium including superoxide, hydrogen peroxide, and hypochlorous acid. In addition, granule contents such as proteolytic enzymes, lysozyme, lactoferrin, and myeloperoxidase are released into the phagosome to destroy ingested microorganisms. Inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, enhance the phagocytic and microbicidal activity of the cells and increase their stickiness. It has been demonstrated in a variety of animal and clinical studies that activated phagocytes can damage the host they are designed to protect, using the mechanisms described above. Alkylxanthines, including pentoxifylline, are potent inhibitors of this inflammatory damage by two major actions: (a) reduction of the production of inflammatory cytokines (especially TNF) by phagocytes stimulated with a variety of microbial products (e.g., endotoxin); and (b) reversal of the effect of these cytokines on phagocytes. Thus, pentoxifylline counteracts the following effects of inflammatory cytokines on phagocytes: increased adherence, shape change resulting in larger size and rigidity, increased oxidative burst, priming for an enhanced oxidative burst, increased degranulation, and decreased chemotactic movement. In addition, these activities synergize with the normal anti-inflammatory mediator adenosine. Alkylxanthines have the potential to be effective therapy for conditions in which inflammatory cytokines and phagocytes cause damage, including the sepsis syndrome, ARDS, AIDS, and arthritis.
 ...
PMID:Cytokines, phagocytes, and pentoxifylline. 869 56