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)

Previous studies have implicated the novel peptide antibiotic human beta-defensin 1 (hBD-1) in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of the second member of this defensin family, human beta-defensin 2 (hBD-2). A cDNA for hBD-2 was identified by homology to hBD-1. hBD-2 is expressed diffusely throughout epithelia of many organs, including the lung, where it is found in the surface epithelia and serous cells of the submucosal glands. A specific antibody made of recombinant peptide detected hBD-2 in airway surface fluid of human lung. The fully processed peptide has broad antibacterial activity against many organisms, which is salt sensitive and synergistic with lysozyme and lactoferrin. These data suggest the existence of a family of beta-defensin molecules on mucosal surfaces that in the aggregate contributes to normal host defense.
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PMID:Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. 972 55

The objective of this study was to determine the expression and production of antimicrobial peptides by healthy and inflamed human synovial membranes. Deposition of the antimicrobial peptides lysozyme, lactoferrin, secretory phospholipase A(2) (sPA(2)), matrilysin (MMP7), human neutrophil alpha-defensins 1-3 (HNP 1-3), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was determined by immunohistochemistry. Expression of mRNA for the antimicrobial peptides bactericidal permeability-increasing protein (BPI), heparin binding protein (CAP37), human cationic antimicrobial protein (LL37), human alpha-defensin 5 (HD5), human alpha-defensin 6 (HD6), HBD-1, HBD-2, and human beta-defensin 3 (HBD-3) was analysed by reverse transcription polymerase chain reaction (RT-PCR). RT-PCR revealed CAP37 and HBD-1 mRNA in samples of healthy synovial membrane. Additionally, HBD-3 and/or LL37 mRNA was detected in synovial membrane samples from patients with pyogenic arthritis (PA), osteoarthritis (OA) or rheumatoid arthritis (RA). BPI, HD5, HD6, and HBD-2 mRNAs were absent from all samples investigated. Immunohistochemistry identified lysozyme, lactoferrin, sPA(2), and MMP7 in type A synoviocytes of all samples. HBD-1 was only present in type B synoviocytes of some of the samples. Immunoreactive HBD-2 peptide was only visible in some inflamed samples. HNP1-3 was detected in both healthy and inflamed synovial membranes. The data suggest that human synovial membranes produce a broad spectrum of antimicrobial peptides. Under inflammatory conditions, the expression pattern changes, with induction of HBD-3 in PA (LL37 in RA; HBD-3 and LL37 in OA) as well as down-regulation of HBD-1. HBD-3 holds therapeutic potential in PA as it has a broad spectrum of antimicrobial activity and accelerates epithelial healing. However, caution is appropriate since defensins also promote fibrin formation and cell proliferation - key elements in joint infection. Clarification of the role of antimicrobial peptides in OA and RA will require further investigation.
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PMID:Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial membranes. 1237 70

The respiratory tract produces a number of molecules that act in the first line of host defense to protect against pathogenic colonization and tissue invasion. Most of the innate antimicrobial activity can be attributed to airway fluid proteins, such as lysozyme, lactoferrin, and secretory leukoproteinase inhibitor, and peptides, such as defensins. Human beta-defensins are cationic antimicrobial peptides with broad and potent microbicidal activity that have been shown to play a role in protecting the healthy lung from infection. To determine the effect of thermal injury on the production of the inducible beta-defensin, human beta-defensin-2 (HBD-2), we measured the concentration of HBD-2 by Western blot analysis in bronchoalveolar lavage samples from the lungs of burned patients with and without inhalation injury. Our data demonstrates an increased amount of HBD-2 in the pulmonary airways with thermal injury compared to normal lung. A further substantial increase in levels was noted in chronic lung conditions.
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PMID:Inducibility of HBD-2 in acute burns and chronic conditions of the lung. 1292 79

The human endometrium is an important site of innate immune defence, giving protection against uterine infection. Such protection is critical to successful implantation and pregnancy. Infection is a major cause of preterm birth and can also cause infertility and ectopic pregnancy. Natural anti-microbial peptides are key mediators of the innate immune system. These peptides, between them, have anti-bacterial, anti-fungal and anti-viral activity and are expressed at epithelial surfaces throughout the female genital tract. Two families of natural anti-microbials, the defensins and the whey acidic protein (WAP) motif proteins, appear to be prominent in endometrium. The human endometrial epithelium expresses beta-defensins 1-4 and the WAP motif protein, secretory leukocyte protease inhibitor. Each beta-defensin has a different expression profile in relation to the stage of the menstrual cycle, providing potential protection throughout the cycle. Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth. The leukocyte populations in the endometrium are also a source of anti-microbial production. Neutrophils are a particularly rich source of alpha-defensins, lactoferrin, lysozyme and the WAP motif protein, elafin. The presence of neutrophils during menstruation will enhance anti-microbial protection at a time when the epithelial barrier is disrupted. Several other anti-microbials including the natural killer cell product, granulysin, are likely to have a role in endometrium. The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.
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PMID:Innate immune defences in the human endometrium. 1464 12

Extensive copy number polymorphism was recently reported for innate immunity-related alpha-defensin genes DEFA1 and DEFA3 and beta-defensin genes DEFB4, DEFB103, and DEFB104. To establish whether such polymorphisms are a common feature of innate immune genes we used quantitative real-time PCR to determine the copy numbers of seven genes whose products have important innate immune functions. The genes encoding lysozyme, lactoferrin, cathelicidin antimicrobial peptide (hCAP18/LL-37), cathepsin G, bactericidal/permeability-increasing protein, azurocidin (CAP37/heparin-binding protein), and neutrophil elastase were each found to be single copy per haploid genome. These findings, along with the recent observation that defensin genes DEFA4, DEFA5, DEFA6, and DEFB1 are single copy, suggest that copy number polymorphisms are not a common feature of the innate immune genome but are restricted to a small subset of innate immunity-related genes.
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PMID:Copy number polymorphisms are not a common feature of innate immune genes. 1661 5

The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.
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PMID:Antimicrobial peptides in the airway. 1690 21

The present study revealed in detail the subcellular localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of beta-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.
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PMID:Immunocytochemical localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotum. 1763 36

The Chinese brown frog (Rana chensinensis) is a special amphibian in northern China, as it has been used widely in traditional Chinese medicine. The skin of the Chinese brown frog is also a promising resource for producing diverse antimicrobial peptides. To obtain a more comprehensive view of the metabolism and effective pharmacological components of Chinese brown frog skin, we constructed a non-normalized cDNA library from the skin. By sequencing cDNA clones at the 5' end, we obtained 5,976 high-quality EST sequences, which clustered into 512 contigs and 1379 singletons (in all 1,891 clusters). After BLAST searches of the protein and nucleic acid databases in GenBank, we found 46.7% of clusters to have significant similarity to known sequences; 28% matched Xenopus tropicalis ESTs and 29.1% matched Xenopus laevis ESTs. Gene annotation results indicated that genes related to secretion and defensive function, such as ubiquitin, lectin, and proteinase inhibitors, are highly expressed in the skin. Whey acidic-domain proteins are also highly abundant in the skin. Furthermore, both a beta-defensin and a lysozyme are transcribed in the frog skin, providing antibacterial protection. Analyses of gene ontology and KEGG metabolic pathways indicated the physiological roles of Chinese brown frog skin.
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PMID:Transcriptome analysis and identification of genes related to immune function in skin of the Chinese brown frog. 1926 15

Psoriasis is a T-cell-mediated skin autoimmune disease characterized by the aberrant activation of dermal dendritic cells (DCs) and the sustained epidermal expression of antimicrobial peptides. We have previously identified a link between these two events by showing that the cathelicidin antimicrobial peptide LL37 has the ability to trigger self-nucleic acid mediated activation of plasmacytoid DCs (pDCs) in psoriatic skin. Whether other cationic antimicrobial peptides exert similar activities is unknown. By analyzing heparin-binding HPLC fractions of psoriatic scales, we found that human beta-defensin (hBD)2, hBD3, and lysozyme are additional triggers of pDC activation in psoriatic skin lesions. Like LL37, hBD2, hBD3, and lysozyme are able to condense self-DNA into particles that are endocytosed by pDCs, leading to activation of TLR9. In contrast, other antimicrobial peptides expressed in psoriatic skin including elafin, hBD1, and psoriasin (S100A7) did not show similar activities. hBD2, hBD3, and lysozyme were detected in psoriatic skin lesions in the vicinity of pDCs and found to cooperate with LL37 to induce high levels of IFN production by pDCs, suggesting their concerted role in the pathogenesis of psoriasis.
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PMID:Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA. 2533 9

In many amniotes, the amniotic fluid is depicted as a dynamic milieu that participates in the protection of the embryo (cushioning, hydration, and immunity). However, in birds, the protein profile of the amniotic fluid remains unexplored, even though its proteomic signature is predicted to differ compared with that of humans. In fact, unlike humans, chicken amniotic fluid does not collect excretory products and its protein composition strikingly changes at mid-development because of the massive inflow of egg white proteins, which are thereafter swallowed by the embryo to support its growth. Using GeLC-MS/MS and shotgun strategies, we identified 91 nonredundant proteins delineating the chicken amniotic fluid proteome at day 11 of development, before egg white transfer. These proteins were essentially associated with the metabolism of nutrients, immune response and developmental processes. Forty-eight proteins were common to both chicken and human amniotic fluids, including serum albumin, apolipoprotein A1 and alpha-fetoprotein. We further investigated the effective role of chicken amniotic fluid in innate defense and revealed that it exhibits significant antibacterial activity at day 11 of development. This antibacterial potential is drastically enhanced after egg white transfer, presumably due to lysozyme, avian beta-defensin 11, vitelline membrane outer layer protein 1, and beta-microseminoprotein-like as the most likely antibacterial candidates. Interestingly, several proteins recovered in the chicken amniotic fluid prior and after egg white transfer are uniquely found in birds (ovalbumin and related proteins X and Y, avian beta-defensin 11) or oviparous species (vitellogenins 1 and 2, riboflavin-binding protein). This study provides an integrative overview of the chicken amniotic fluid proteome and opens stimulating perspectives in deciphering the role of avian egg-specific proteins in embryonic development, including innate immunity. These proteins may constitute valuable biomarkers for poultry production to detect hazardous situations (stress, infection, etc.), that may negatively affect the development of the chicken embryo.
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PMID:The Unique Features of Proteins Depicting the Chicken Amniotic Fluid. 2944 82


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