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 test our hypothesis that neutrophil elastase plays a role in airway hypersecretion associated with the allergic late-phase response, using an isolated tracheal segment system in vivo and measuring lysozyme activity in the perfusate of the lumen as a marker of submucosal gland secretion over 8 h, we studied the response of five allergic dogs to ragweed. The dogs were exposed on separate occasions to specific allergen, to allergen vehicle, and to allergen in the presence of a selective neutrophil elastase inhibitor, ICI 200,355. Allergen exposure caused a marked increase in lysozyme secretion that was significantly increased at 4, 6, and 8 h compared with controls and ICI 200,355-treated dogs. Neutrophil elastase appeared in the perfusate after allergen exposure and was positively correlated with lysozyme secretion at 8 h. These findings suggest that neutrophil elastase plays an important role as a secretagogue in the allergic late-phase response.
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PMID:Role of neutrophil elastase in allergen-induced lysozyme secretion in the dog trachea. 139 99

The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
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PMID:Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. 147 6

Human alveolar macrophages from lungs of cigarette smokers were retrieved by lavage of surgical specimens. The macrophage secretions were harvested after 18 h of incubation. The medium contained at least 2 acid-stable factors that could release enzymes from cytochalasin-B-treated human neutrophils. Our study focused on the largest of these factors, which had an apparent mass ratio of 5,400 by gel filtration chromatography in 10% acetic acid. The high molecular weight (HMW) factor was partially degraded by trypsin. Chymotrypsin completely destroyed the factor, but human neutrophil elastase did not affect it. The factor is partially extractable into chloroform indicating that it is very hydrophobic and may contain a lipid. High concentrations of the HMW factor inhibited the release of lysozyme and myeloperoxidase. Because elastases can cause emphysema when introduced into alveoli of animals, the most important observation may be that the HMW factor was able to release elastase from human neutrophils attached to Millipore membranes in the absence of cytochalasin B. The enzyme-releasing factors may be identical to neutrophil chemotactic factors recently described by others. The contribution of the released elastase to the protease load in the lung may be augmented by the simultaneous release from neutrophils of myeloperoxidase, which can inactivate alpha 1-antitrypsin. This interaction between alveolar macrophages and neutrophils may have importance in the pathogenesis of emphysema.
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PMID:The release of elastase, myeloperoxidase, and lysozyme from human alveolar macrophages. 628 85

The proteinase "inhibitor" alpha 2-macroglobulin (alpha 2M) is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. These complexes are rapidly endocytosed after binding to receptors present on macrophages and other cells. We have previously shown that compared to free hen egg lysozyme (HEL), alpha 2M-complexed HEL undergoes enhanced macrophage uptake, processing, and presentation to T hybridoma clones in vitro. Inasmuch as it is not clear whether T hybridoma responses accurately reflect primary immune responses in vivo, we studied antibody production in rabbits using two Ag complexed with either human alpha 2M (H alpha 2M) or a homologous protein purified from rabbit plasma, alpha 1-macroglobulin (R alpha 1M). Pathogen-free NZW rabbits received s.c. injections with adjuvant-free preparations of free HEL or porcine pancreatic elastase (PPE), H alpha 2M-HEL-PPE complexes, R alpha 1M-HEL-PPE complexes, or mixtures of the uncomplexed proteins. Complexing the Ag to alpha 2M resulted in 10 to 500-fold higher IgG titers compared to uncomplexed controls. Injection of Ag complexed to either H alpha 2M or R alpha 1M resulted in levels of anti-HEL IgG comparable to those elicited by emulsification in CFA. Inasmuch as inflammatory proteinases such as neutrophil elastase can initiate covalent complex formation with alpha 2M, we propose that "proteinase-activated" alpha 2M may mediate receptor-enhanced Ag uptake by macrophages, resulting in augmented Ag processing and antibody production.
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PMID:Adjuvant-free in vivo targeting. Antigen delivery by alpha 2-macroglobulin enhances antibody formation. 750 26

A systematic morphological analysis of cutaneous infiltrates in acute myelogenous leukemia and myelodysplastic syndrome revealed that in many cases the infiltrating cells have a different phenotype from those in the bone marrow. This study sought to answer two questions: (a) How wide is the range of cytological features and immunoreactivity of the cutaneous infiltrates and what danger is there of misinterpretation? (b) What are the possible causes of the wide spectrum of differentiation of the cells infiltrating the skin? Skin biopsy specimens from 16 patients with myelogenous leukemia or myelodysplastic syndrome were investigated. The diagnosis was acute myelomonocytic leukemia (M4, according to the French-American-British/FAB system of classification of acute leukemias) in eight cases, acute monocytic leukemia (M5) in four cases, aleukemic leukemia cutis as a recurrence of M2 leukemia after treatment in one case, and myelodysplastic syndrome in three cases, including one case of myelodysplasia with an excess of bone marrow blasts (RAEB-T) and two cases of chronic myelomonocytic leukemia, one of which presented as aleukemic leukemia cutis. Reactivity with the macrophage-associated antibodies anti-CD68, Ki-M1p, and anti-lysozyme was the most consistent. However, the naphthol AS-D chloroacetate esterase reaction and staining with DAKO-M1, Ki-My2p, anti-neutrophil elastase, and anti-CD34 were found to be of little value for identifying the cutaneous infiltrate as myelogenous. Some antibodies (e.g., anti-S100 protein and MB2) even produced staining in a few cases that could have led to a mistaken diagnosis of histiocytic neoplasm or malignant lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skin involvement in myelogenous leukemia: morphologic and immunophenotypic heterogeneity of skin infiltrates. 754 88

The value of immunohistochemical staining in the subtyping of acute leukemia was investigated on 36 routinely processed (formalin-fixed and paraffin-embedded) trephine biopsy specimens from the iliac crest containing diffuse infiltrates of acute myelogenous leukemia (AML; n = 23) and acute lymphoblastic leukemia (ALL; n = 13). These were stained with a broad panel of antibodies (n = 23) against various leukocyte antigens, among them 11 macrophage-associated antibodies (MAAs): Ki-M1p, MAC387, HAM56, LN5, KP1 (CD68), PG-M1 (CD68), Ki-M4p, DAKO-DRC (CD35), and antibodies against lysozyme, alpha 1-antichymotrypsin, and S100 protein. The French-American-British (FAB) classification subtypes of the AML cases, as determined by enzyme-cytochemical and/or immunocytological investigation of bone marrow smears, were as follows: M1 = 6, M2 = 5, M4 = 7, M5 = 3, and AML (not classified) = 2. The 13 cases of ALL were classified as follows: c-ALL (pre-B-ALL) = 7, B-ALL = 3, T-ALL = 2, and ALL (not classified) = 1. All the MAAs except LN5, Ki-M4p, and DAKO-DRC stained blast cells in AML. However, the number of stained blast cells varied considerably within and between the individual subtypes (M4/5 > M2/1). Using Fisher's exact test a significant difference in frequency of blast cell staining between AML and ALL was found for four MAAs (anti-lysozyme, MAC387, Ki-M1p, and KP1) and two of the three myeloid cell markers applied (Ki-My2p and anti-neutrophil elastase). Of these six antibodies, the combination of anti-lysozyme and KP1 can be recommended for use in routine diagnostics for the differentiation of AML from ALL on the basis of immunohistochemical staining because both of these antibodies were found to stain a relatively large percentage of cases of AML but none of ALL. However, none of the MAAs were found to discriminate reliably between the FAB M4/5 and M1/2 subtypes of AML.
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PMID:Assessment of the value of immunohistochemistry in the subtyping of acute leukemia on routinely processed bone marrow biopsy specimens with particular reference to macrophage-associated antibodies. 805 22

Airway inflammation is often associated with the infiltration of activated neutrophils and subsequent protease release. Although aiding in the digestion and phagocytosis of foreign proteins and microorganisms, neutrophil proteases can indiscriminately damage healthy lung tissue. In the conducting airway, proteases, particularly neutrophil elastase, are counter-balanced by several antiproteases, including secretory leukocyte protease inhibitor (SLPI). SLPI can be produced locally by a number of cells including the airway epithelial cell. To examine the effects of neutrophil granule components on SLPI transcript levels, airway epithelial cells were treated (up to 96 h) with elastase, other proteases, or enzymes isolated from human sputum. We found that neutrophil elastase increased SLPI transcript levels in primary and transformed human airway epithelial cells in a time- and dose-dependent manner. Other neutrophil products, such as cathepsin G, myeloperoxidase, and lysozyme, had little or no effect on SLPI transcript levels. However, two nonneutrophil proteases, trypsin and pancreatic elastase, also increased SLPI transcript levels at higher doses than that required of neutrophil elastase. Two inflammatory cytokines, tumor necrosis factor-alpha and interleukin-8, produced little or no effect on SLPI transcript levels. This study demonstrates one way in which SLPI is regulated, via a protease that it inhibits, neutrophil elastase.
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PMID:Neutrophil elastase increases secretory leukocyte protease inhibitor transcript levels in airway epithelial cells. 810 97

alpha 1-Antitrypsin (alpha 1-AT) is an acute phase plasma protein predominantly derived from the liver which inhibits neutrophil elastase. Previous studies have suggested that alpha 1-AT is also expressed in human enterocytes because alpha 1-AT mRNA could be detected in human jejunum by RNA blot analysis, and alpha 1-AT synthesis could be detected in a human intestinal adenocarcinoma cell line Caco2, which spontaneously differentiates into villous-like enterocytes in tissue culture. To definitively determine that the alpha 1-AT gene is expressed in human enterocytes in vivo, we examined tissue slices of human jejunum and ileum by in situ hybridization. The results demonstrate specific hybridization to enterocytes from the bases to the tips of the villi. Although there was no hybridization to enterocytes in most of the crypt epithelium, there was intense specific hybridization in one region of the crypt. Double-label immunohistochemical studies showed that alpha 1-AT and lysozyme co-localized to this region, indicating that it represented Paneth cells. Finally, there was a marked increase in hybridization to alpha 1-AT mRNA in villous enterocytes and Paneth cells in Crohn's disease. The results of this study provide definitive evidence that alpha 1-AT is expressed in human jejunal and ileal enterocytes in vivo, and show that alpha 1-AT is also a product of Paneth cells. Together with the results of other studies, these data raise the possibility that alpha 1-AT detected in fecal alpha 1-AT clearance assays for diagnosing protein-losing enteropathies is predominantly derived from sloughed enterocytes.
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PMID:Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium. 840 56

The distribution of the lysosomal enzymes cathepsin B, lysozyme, chymotrypsin, and neutrophil elastase was examined in eccrine, apocrine, and sebaceous glands using a postembedding immunogold labeling procedure. Various amounts of cathepsin B were detected in all glands. Lysozyme, however, was detected in apocrine glands only. The other two lysosomal enzymes were not detectable immunologically. In apocrine and eccrine glands, anti-cathepsin B antibody labeled all secretory granules. In sebaceous glands, only the peripheral layer of cells showed immunological activity for cathepsin B. In apocrine glands, granules containing remnants of cristae were more intensively labeled than those lacking cristae which supports the assumption that both granules are derived from mitochondria by acquiring lysosomal enzymes. The enzymes convert mitochondria to granules with cristae and finally to granules without cristae. Thus the difference in morphology is part of a spectrum of the degradation of mitochondria to granules.
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PMID:Immunelectron microscopic localization of cathepsin B in human exocrine glands. 846 18

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.
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PMID:Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries. 853 74


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