Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intratracheal instillation of human neutrophil elastase (HNE) causes accumulation of an excess number of secretory granules in the epithelial secretory cells lining the hamster bronchus. This chronic lesion, which we refer to as secretory cell metaplasia (SCM), is not seen in the trachea or bronchioles. Because luminal cell surface lectin binding is much higher in the trachea than in the bronchus, we concluded that tracheal resistance may be due to a protective glycoconjugate coat. In the present ultrastructural study, we analyzed the lectin-binding capability of bronchiolar epithelial cells to determine whether their luminal cell surface glycoconjugate layer is similar to tracheal epithelial cells. None of the six ferritin-conjugated lectins showed higher binding in bronchioles compared to the bronchus, suggesting that a high level of surface oligosaccharides is not necessary for resistance to the metaplastic effects of HNE. HNE caused a significant reduction in bronchiolar surface binding of the gold-labeled, secretory cell-specific lectin, Helix pomatia agglutinin. The principal granulated secretory cell type in bronchioles was ultrastructurally similar to a form of bronchial Clara cell that converts to a mucous cell phenotype in response to HNE. The results suggest that absence of bronchiolar SCM is not attributable to a protective layer of cell surface oligosaccharides, a lack of cellular contact by HNE, or the presence of a morphologically distinct population of epithelial cells in bronchioles.
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PMID:Resistance of hamster bronchiolar epithelium to neutrophil elastase: investigation by cell surface lectin cytochemistry. 157 19

We studied the effect of aminosugars on the elastase enzyme released from cytochalasin-B treated polymorphonuclear neutrophils (PMN) and stimulated by F-Met-Leu-Phe (FMLP). Both N-acetyl-galactosamine and N-acetyl-glucosamine can inhibit the release of leukocyte elastase enzyme. N-acetyl-galactosamine was a potent inhibitor of elastase enzyme release in a dose-related fashion. Inhibition ranged from 91.9% up to total inhibition. N-acetyl-glucosamine showed a mild inhibitory effect on elastase enzyme release; however, it too acted in a dose-related fashion. The range of inhibition was 17.17%-8.18%. Mannosamine showed an inhibitory effect in some donors, but this effect was not statistically significant. No effect on elastase enzyme release was shown with other sugars such as D-glucose and L-fucose. These results show that N-acetyl-galactosamine can inhibit the respiratory burst, which suggests that the aminosugars might do more than interfere with the carbohydrate lectin interaction.
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PMID:Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine. 205 63

Hamsters exposed to an intratracheal instillation of human neutrophil elastase (HNE) accumulate an abnormally high number of secretory granules in bronchial but not tracheal epithelial cells. We employed lectin cytochemistry to investigate possible differences in the epithelial cell surface glycoconjugate layer in trachea compared to bronchus which might explain the regional dissimilarity in response to HNE. Portions of glutaraldehyde-fixed trachea and bronchi were incubated in one of several ferritin-labeled lectins prior to embedding for transmission electron microscopy. Lectins from Ricinus communis, Helix pomatia, and Triticum vulgaris bound to the surface of tracheal secretory cells in moderate to profuse amounts, while most bronchial secretory cells showed little or no label with these lectins. Gold-labeled Helix pomatia agglutinin (HPA), a lectin specific for secretory cells, showed a decrease in surface binding to all tracheal secretory cell types within 2 h of HNE instillation, compared to saline controls. In contrast, the majority of bronchial secretory cells showed an HNE-induced increase in surface label from extremely low levels in saline controls. The low levels of lectin binding to bronchial cells, in contrast to the trachea, may indicate the lack of a protective surface glycoconjugate coat, thus explaining the vulnerability of these cells to HNE. The rise in number of accessible HPA binding sites on the surface of bronchial secretory cells exposed to HNE may represent an important event in the pathologic accumulation of secretory granules by these cells.
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PMID:Lectin cytochemistry reveals differences between hamster trachea and bronchus in the composition of epithelial surface glycoconjugates and in the response of secretory cells to neutrophil elastase. 236 36

The macrophage has been shown to bind potentially pathogenic bacteria in the absence of serum components or opsonins but the mechanism is poorly understood. The rich array of sugars on the surface of group B streptococci plus the presence of membrane-associated lectin receptors on the macrophage suggests that this is a likely means for bacterial recognition by these host defense cells. Inhibition studies with free sugars and neoglycoconjugates of bovine serum albumin, however, failed to confirm this hypothesis. Furthermore, neuraminidase-treatment to expose galactose residues and the use of isogenic bacterial strains having no capsule or no capsular sialic acid yielded no confirmation of lectin-mediated recognition. The trypsin-sensitive receptor exhibited temperature dependence and a requirement for divalent cations distinct from that reported for the lectin-like galactose receptor. The activity of this streptococcal binding receptor was inhibited by 2-deoxy-D-glucose but not by neutrophil elastase. Pre-exposure of macrophages to bound fibronectin and treatment with phorbol ester each enhanced bacterial binding. These data fail to support a role for the galactose lectin and provide preliminary evidence for involvement of the leukocyte integrins in macrophage recognition of group B streptococci.
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PMID:Characterization of the murine macrophage receptor for group B streptococci. 835 25

Bronchial mucous cell metaplasia (MCM) is a histologic component of chronic mucus hypersecretion. The hamster model of elastase-induced MCM appears to involve an irreversible conversion of Clara cells to mucous cells. The present study questioned whether the mucous cells seen in hamster bronchi exposed to neutrophil elastase produce and maintain a form of glycoconjugate secretory product different from that normally found in mucous cells or Clara cells. Ultrastructural cytochemistry using the gold-labeled lectin HPA revealed a difference in the cell surface and stored secretory granules of elastase-derived mucous cells compared to normal mucous cells and Clara cells at 3 weeks and 4 months following exposure. The results suggest that elastase irreversibly alters the glycoconjugate character of the Clara cells normally present so that they produce an abnormal form of mucus. Because secreted glycoconjugates can affect the rate of mucociliary clearance and receptor-mediated binding of microorganisms, this change in phenotype may be involved in the pathogenesis of diseases associated with chronic mucus hypersecretion in humans.
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PMID:Abnormal mucous cell phenotype induced by neutrophil elastase in hamster bronchi. 920 55

Mucin is the major component of mucus and can be used as a marker for mucus secretion. The purpose of this study was to develop an in vitro method to evaluate the regulation of mucin secretion. To do this, we used a sandwiched enzyme-linked lectin assay to measure mucin secretion from isolated ferret tracheal segments. This assay entailed coating microtiter plate wells with dolichos biflorus agglutinin and detecting the bound mucin that was secreted into a buffer solution by the tracheal segments. We used this method to evaluate the secretory response to four secretagogues: prostaglandin F2alpha (PGF2alpha), adenosine triphosphate (ATP), methacholine, and human neutrophil elastase (HNE). Each agent stimulated mucin secretion above baseline secretion (ATP (p = 0.022), PGF2alpha (p = 0.009), and HNE (p < 0.05)), and the relative potency of these secretagogues was PGF2alpha < or = ATP < MCh < HNE. We also demonstrated that there is an anatomic gradient for both constitutive and stimulated mucin secretion, with the distal tracheal segments secreting more mucin per gram of weight than the proximal segments. This fairly simple and reproducible technique can be used to evaluate the regulation of mucin secretion in the airway and to assess the efficacy of agents that might alter the secretory response.
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PMID:Regulation of mucin secretion in the ferret trachea. 937 71

Mucus hypersecretion is an important characteristic of many airway diseases. Mucin is the major component of mucus, and is secreted from surface goblet cells of the airway epithelium and mucous cells of submucosal glands. Lysozyme is an enzyme secreted by serous cells of airway submucosal glands. We hypothesized that secretagogues acting through different pathways would have different effects on tracheal mucin and lysozyme secretion. We used a sandwich enzyme-linked lectin assay (ELLA) to measure mucin-like glycoprotein secretion and a spectrophotometric method to measure lysozyme secretion from isolated ferret tracheal segments. We evaluated the secretory response to four secretagogues; prostaglandin F(2alpha) (PGF(2alpha)), adenosine triphosphate (ATP), methacholine (MCh), and human neutrophil elastase (HNE). Each agent stimulated mucin and lysozyme secretion. The relative potency was PGF(2alpha)< or =ATP<MCh<HNE for mucin and ATP< or =PGF(2alpha)<MCh<HNE for lysozyme secretion. We showed that there is an anatomic gradient for constitutive and stimulated mucin and lysozyme secretion with the distal tracheal segments secreting more mucin and lysozyme per gram of tissue than the proximal segments. This robust model system can be used to evaluate the regulation of airway mucous and serous cell secretion and to assess the effect of agents that might alter the secretory response. We confirm that on an equimolar basis, HNE is one of the most potent mucus secretagogues.
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PMID:Regulation of secretion from mucous and serous cells in the excised ferret trachea. 1134 43

Surfactant protein D (SP-D) is a multimeric collagenous lectin that mediates the clearance of pathogens and modulates immune cell functions via its C-terminal carbohydrate recognition domain (CRD). We hypothesized that extracellular proteolysis of SP-D may result in a loss of its functional properties. Multimeric SP-D was partially digested by human leukocyte elastase (HLE) dose- and time-dependently. Physiologic concentrations of calcium slowed, but did not protect from degradation. In solution, both native and degraded SP-D had an apparent molecular weight of 650 to >1000 kDa. Under reducing conditions, the degraded SP-D monomers run at 10 kDa less than native SP-D. Amino acid sequencing located all major cleavage sites into the CRD. Functional studies showed that degraded SP-D had lost its calcium-dependent lectin properties, i.e. neither bound to mannose nor agglutinated bacteria. These studies demonstrate that elastase results in the limited proteolysis of SP-D with loss of its CRD-dependent activities and suggest that proteases at concentrations observed in various lung diseases may impair the antimicrobial and immunomodulatory roles of SP-D.
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PMID:Limited proteolysis of surfactant protein D causes a loss of its calcium-dependent lectin functions. 1285 21

Tamm-Horsfall glycoprotein (THP), the most abundant protein in mammalian urine, has been implicated in defending the urinary tract against infections by type 1-fimbriated Escherichia coli. Recent experimental evidence indicates that the defensive capability of THP relies on its single high mannose chain, which binds to E. coli FimH lectin and competes with mannosylated uroplakin receptors on the bladder surface. Here we describe several major differences, on both structural and functional levels, between human THP (hTHP) and pig THP (pTHP). pTHP contains a much higher proportion (47%) of Man5GlcNAc2 than does hTHP (8%). FimH-expressing E. coli adhere to monomeric pTHP at an approximately 3-fold higher level than to monomeric hTHP. This suggests that the shorter high mannose chain (Man5GlcNAc2) is a much better binder for FimH than the longer chains (Man6-7GlcNAc2) and that pTHP is a more potent urinary defense factor than hTHP. In addition, unlike hTHP whose polyantennary glycans are exclusively capped by sialic acid and sulfate groups, those of pTHP are also terminated by Galalpha1,3Gal epitope. This is consistent with the fact that the outer medulla of pig kidney expresses the alpha1,3-galactosyltransferase, which is completely absent in human kidney. Finally, pTHP is more resistant to leukocyte elastase hydrolysis than hTHP, thus explaining why pTHP is much less prone to urinary degradation than hTHP. These results demonstrate for the first time that the species variations of the glycomoiety of THP can lead to the differential binding of THP to type 1-fimbriated E. coli and that the differences in high mannose processing may reflect species-specific adaptation of urinary defenses against E. coli infections.
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PMID:Variation of high mannose chains of Tamm-Horsfall glycoprotein confers differential binding to type 1-fimbriated Escherichia coli. 1457 Aug 81

Quantitative changes in plasma protein concentrations during tissue injury or inflammation (acute phase response) are often accompanied by specific alterations in the carbohydrate moieties of these proteins. The glycosylation changes comprise alterations in the type of branching of the carbohydrate structures as revealed by modulated reactivity of acute phase glycoproteins with the lectin concanavalin A. Interestingly, inflammation-induced changes in the glycosylation of acute phase proteins have been shown to affect the functional properties of these proteins. In this study we demonstrate that synthesis of acute phase protein alpha(1)-PI, the controlling inhibitor of neutrophil elastase, is significantly up-regulated in hepatic and lung-derived epithelial cells by the inflammatory mediator oncostatin M. Although oncostatin M markedly altered the concanavalin A reactivity of hepatic alpha(1)-PI, lung-derived epithelial cells did not change the pattern of alpha(1)-PI glycan branching upon stimulation with oncostatin M. These results indicate that inflammation-induced changes in glycosylation of alpha(1)-PI may have different impacts on functional properties of liver and lung-synthesized alpha(1)-PI.
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PMID:Acute phase mediator oncostatin M regulates affinity of alpha1-protease inhibitor for concanavalin A in hepatoma-derived but not lung-derived epithelial cells. 1592 52


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