Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the secretory products and the proliferation of cells of the human respiratory surface epithelium, we established a miniorgan-culture system of bronchial tissue. Biopsies of large airways were grown on agar-coated dishes immersed in a serum-enriched medium. As determined by light and transmission electron microscopy, between 1 and 3 weeks, the organ cultures were covered by a differentiated epithelium consisting of secretory, ciliated, and basal cells. Immunohistochemistry, using antibodies to mucin and lysozyme, and lectin histochemistry revealed both mucous and serous secretory cells in the epithelium. Cell proliferation was studied in situ using antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. Whereas at the time of explantation the proliferation was low (2.5+/-1.7% of the epithelial cells were PCNA-positive, 1.7+/-0.6 were Ki-67-positive), at 24 h of cultivation, 30.4+/-5.1% or 25.2+/-4.9% of the epithelial cells were labeled with antibodies to PCNA or Ki-67. After 7 days, the number of dividing cells was low again. The results show that the organ-culture system of human respiratory surface epithelium produces a differentiated epithelium that is useful in the study of secretory processes, differentiation, and proliferation.
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PMID:Secretory cell types and cell proliferation of human bronchial epithelial cells in an organ-culture system. 971 48

Human acinic cell adenocarcinoma cell (HACC) line was established from the pleural effusion that contains metastatic tumor cells of acinic cell adenocarcinoma of papillary and microcystic type originating from the parotid gland. The HACC cells grew in an adherent monolayer with a doubling time of 66 h. Implanted tumor of SCID mice revealed similar histological findings to that of the primary tumor. The HACC cells produced mucin and expressed epithelial markers as well as alpha1-antitrypsin and lysozyme, whereas salivary peptide P-C was expressed in cultured HACC cells but not in the primary and implanted HACC cell tumors. S-100 protein was also expressed in both the primary tumor and HACC cell line. Neither amplification of common oncogenes nor expression of p53 was observed. The receptor for epidermal growth factor (EGF) was expressed, indicating EGF and transforming growth factor-alpha (TGF-alpha) enhanced the growth of the HACC line. Unexpectedly, tumor necrosis factor-a (TNF-alpha) also enhanced the growth of the HACC line significantly. However, there was no evidence of autocrine growth using these growth factors. In contrast, TGF-beta1 inhibited the growth of the HACC cell line through apoptosis. The HACC cell line has features similar to both acinar and intercalated ductal cells of the salivary gland. Epidermal growth factor, TGF-alpha and TNF-alpha are potential growth factors for the HACC cell line. The HACC cell line may be a good model for studying the biological behavior of salivary gland neoplasms.
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PMID:Characterization of a newly established human acinic cell adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line. 978 63

The mammalian reovirus sigma1 protein is responsible for viral attachment to host cells and hemagglutination properties of the virus. In the present study, sequence similarity between sigma1 and chicken-type lysozymes prompted us to investigate additional functions of the sigma1 protein. Expression in Pichia pastoris yeast cells showed that sigma1 can actually cleave lysozyme substrates, including complex sugars found in bacterial cell walls. Replacement by site-directed mutagenesis of acidic amino acid residues in sigma1 by their respective isosteric, uncharged, amino acid residues has allowed us to identify Glu36 and Asp54 as the catalytic pair involved in sigma1-mediated glycosidase activity. The enzyme appears inactive in virions but its activity is unmasked upon generation of infectious subviral particles (ISVPs) by partial proteolytic removal of the outer capsid proteins. Purified sigma1 protein and ISVPs can also hydrolyze mucins, heavily glycosylated glycoproteins that are a major component of the mucus layer overlaying the intestinal epithelium. Furthermore, reovirus infection of epithelial Madin Darby canine kidney cells was inhibited tenfold in cells expressing mucin at their apical surface, while this inhibition was overcome by ISVPs. Unmasking of sigma1 mucinolytic activity in the intestine, consecutive to proteolytic cleavage of virions to ISVPs, thus likely contributes to the known increase in infectivity of reovirus ISVPs compared to complete virions. This work presents the first evidence that some mammalian viruses have evolved mechanisms to facilitate their penetration through the protective barrier of the mucus layer in the intestinal tract.
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PMID:A glycosyl hydrolase activity of mammalian reovirus sigma1 protein can contribute to viral infection through a mucus layer. 1002 49

It has long been assumed that unstimulated tears are more thoroughly equilibrated with epithelial secretions than stimulated tears, since they are in contact with tarsal, bulbar and corneal surfaces for longer. It was also believed from results with model solutions that soluble mucin is responsible for the observed surface tension and viscosity of tears. If longer contact means more mucin is dissolved in the aqueous tears, then the surface activity (surface tension lowered by mucin) and viscosity (raised by mucin) of tears should therefore be enhanced in unstimulated over stimulated tears. Pools of stimulated and minimally-stimulated tears were collected from a group of healthy adult volunteers by glass capillary. Viscosities were measured in the Contraves Low Shear 30 rheometer over the range of shear rates 0-130 sec-1. Surface tension was measured in the collection capillaries by a micro-technique, before and after refrigerated storage. Both surface tension and viscosity were determined for a variety of tear proteins and mucins. No significant difference was found between the viscosity/shear rate plots of stimulated and unstimulated tear samples. The viscosities of solutions of individual tear proteins were low, except for the combination of lysozyme and secretory IgA. Surface tensions were also similar in both cases, and unchanged by storage at room temperature or refrigeration, indicating no significant loss of surface-active material by adsorption on the capillary walls. Results with model mucin solutions gave a variety of results indicating either little surface activity or losses due to wall adsorption. Tear proteins, individually or in combination, did not lower surface tension to the level of tears. Tear viscosity seems not to depend on the level of dissolved mucins. This suggests either that a constant level of these is picked up even by short-term contact with ocular surfaces, or that viscosity arises from currently unknown materials which vary little with tear flow rate. This type of shear-dependent viscosity is most easily simulated in model solutions with polyionic linear macromolecules, including mucins. The contribution of individual proteins to overall viscosity is small, but combinations including lysozyme show tear-like characteristics, and may indicate that proteins whose concentration is relatively independent of tear flow rate combine with other tear components (possibly including mucins or lipids) to produce their full effect on tear viscosity. The surface tension results suggest that mucins are not of primary importance. Theories of tear film structure and performance need revision.
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PMID:Physical properties of stimulated and unstimulated tears. 1006 90

We previously reported (Gray, T. E., K. Guzman, C. W. Davis, L. H. Abdullah, and P. Nettesheim. 1996. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 14:104-112) that retinoic acid (RA)-deprived cultures of normal human tracheobronchial epithelial (NHTBE) cells became squamous, failed to produce mucin, and instead secreted or released large amounts of lysozyme (LZ). The purpose of the studies reported here was to elucidate the relationship between RA deficiency-induced squamous differentiation and increased LZ, and to determine what mechanisms were involved. We found that intracellular LZ began to accumulate in RA-deficient NHTBE cultures early during squamous differentiation. Between Days 10 and 18 of culture, cellular LZ levels were more than 10 times higher in RA-deficient than in RA-sufficient cultures. On Day 12, large numbers of cells began to exfoliate in RA-deficient cultures and extracellular LZ appeared at the apical surface, presumably released from the exfoliated cells. Metabolic labeling studies showed that the rate of LZ synthesis was not increased in RA-deficient cultures over that in RA-sufficient cultures; however, intracellular LZ half-life was much longer in RA-deficient cultures. We concluded that the increased accumulation of both intra- and extracellular LZ in RA-deficient cultures was due to increased LZ stability and was not the result of increased LZ synthesis. When RA-deficient cultures were treated on Day 7 with 10(-6) M RA, intracellular LZ levels did not substantially decrease until 3 d later, coinciding with a marked increase in mucin secretion. LZ messenger RNA levels were unchanged at 24 h, but were modestly increased (rather than decreased) at all subsequent time points. We concluded that RA does not directly regulate LZ, and that the excessive accumulation of LZ in RA-deprived NHTBE cells is a consequence of vitamin A deficiency-induced abnormal differentiation.
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PMID:Lysozyme expression during metaplastic squamous differentiation of retinoic acid-deficient human tracheobronchial epithelial cells. 1010 Sep 88

Airway mucus hypersecretion is in part a response to infection and inflammation. Pseudomonas aeruginosa infection is nearly universal in advanced cystic fibrosis (CF) lung disease. Mucoid strains of P. aeruginosa produce an exopolysaccharide product called alginate. The purpose of this study was to determine whether P. aeruginosa alginate stimulates secretion from mucous or serous cells in the ferret trachea exposed to alginate at concentrations reported to be present in the CF airway. We used a sandwich enzyme-linked lectin assay (ELLA) to measure mucin secretion and spectrophotometry to measure lysozyme secretion from isolated ferret tracheal segments. Purified Pseudomonas aeruginosa alginate stimulated mucin and lysozyme secretion in a dose-dependent fashion (mucin = +111%: P = 0.003; lysozyme = +20%: P = 0.024 at 200 microg/mL). This stimulated secretion was not due to proteolytic activity, and alginate exposure did not produce ultrastructural damage to the trachea. We conclude that alginate may contribute to mucus hypersecretion and respiratory morbidity associated with P. aeruginosa infection in patients with CF.
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PMID:Pseudomonas aeruginosa alginate is a potent secretagogue in the isolated ferret trachea. 1021 55

Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing infection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of the CF airway. We found that abundant airway antimicrobial factors kill common CF pathogens, although Burkholderia was relatively resistant. To study the antibacterial activity, we developed a rapid, sensitive, and quantitative in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inhibited by high ionic strength, and it was particularly sensitive to divalent cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be partially compensated by increased concentrations of antibacterial factors, thus there was no one unique salt concentration for inhibition. CF airway secretions also contain abundant mucin and elastase; however, these had no effect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fluids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results suggest approaches toward developing treatments aimed at preventing or reducing airway infections in individuals with CF.
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PMID:Activity of abundant antimicrobials of the human airway. 1022 57

We describe a 61-year-old woman who presented with multiple small, firm, shiny, skin-coloured papules in a symmetrical pattern on the dorsum of the hands, sides of the fingers and extensor aspect of the forearms. These had slowly increased in number over a period of 40 years, and were asymptomatic. Both laboratory results and systemic review were unremarkable. Histological examination of six papules revealed well-circumscribed but unencapsulated dermal nodules composed of epithelioid histiocytes and abundant alcian blue-positive mucin separating broad bundles of collagen. Histiocytes within the nodule stained positively with vimentin, and were focally positive for alpha1-antitrypsin and lysozyme. The interstitium was positive for tenascin. On electron microscopy, the histiocytes showed numerous circular, osmophilic myelin bodies and zebra bodies reminiscent of those seen in lysosomal storage diseases. Our patient's clinical, histological and ultrastructural features have been previously described as hereditary progressive mucinous histiocytosis, a rare familial form of eruptive histiocytoma characterized by multiple persistent papules with prominent mucinosis.
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PMID:Hereditary progressive mucinous histiocytosis. 1060 60

Histochemical staining has shown that so-called adenoma malignum (the mucinous type of minimal deviation adenocarcinoma [mucinous MDA]) of the uterine cervix expresses gastric phenotypes. The present ultrastructural study was undertaken to explore the fine structure and phenotypic expression of this tumor, and to make comparisons with normal cervical glands and gastric pyloric mucosa. Post-embedding, double-immunogold staining for gastric gland mucous cell mucin (HIK1083-reactive mucin) and lysozyme revealed localization exclusively to the matrix and to the core of the mucin granules, respectively, both in mucinous MDA and gastric pyloric mucosa. Mucin granules of normal cervical gland cells lacked core structures and showed no immunoreactivity with HIK1083 or lysozyme. Thus, mucinous MDA was confirmed to be a tumor expressing gastric phenotypes ultrastructurally. Both markers should be useful for the identification of tumor cells.
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PMID:Ultrastructural features of adenoma malignum of the uterine cervix: demonstration of gastric phenotypes. 1062 87

Human and animal exposure to particulate air pollution is correlated with airway mucus hypersecretion and increased susceptibility to infection. Seeking clues to the mechanisms underlying this pathology, we examined the effect of the particulate air pollutant residual oil fly ash (ROFA) on production of the major component of mucus, mucin, and the major antibacterial protein of the respiratory tract, lysozyme. We found that following in vitro exposure to ROFA, epithelial cells showed an increase in mucin (MUC5AC) and lysozyme (LYS) steady state mRNA. This upregulation was controlled at least partly at the level of transcription as shown by reporter assays. Experiments testing the ability of the major components of ROFA to mimic these effects showed that vanadium, a metal making up 18.8% by weight, accounted for the bulk of the response. A screen of signaling inhibitors showed that MUC5AC and LYS induction by ROFA are mediated by dissimilar signaling pathways, both of which are, however, phosphotyrosine dependent. Recognizing that the ROFA constituent vanadium is a potent tyrosine phosphatase inhibitor and that mucin induction by pathogens is phophotyrosine dependent, we suggest that vanadium-containing air pollutants trigger disease-like conditions by unmasking phosphorylation-dependent pathogen resistance pathways.
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PMID:Lung mucin production is stimulated by the air pollutant residual oil fly ash. 1063 31


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