Antileukoprotease in Human Skin: An Antibiotic Peptide Constitutively Produced by Keratinocytes

Wiedow, Oliver; Harder, Jürgen; Bartels, John; Streit, Volker; Christophers, Enno

doi:10.1006/bbrc.1998.9069

Cited by 158 publications

(116 citation statements)

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“…PGLYRPs require Ca 2ϩ and N-glycosylation for bactericidal activity, which are not usually required by membrane-permeabilizing antibacterial peptides, such as defensins or magainin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). PGLYRPs are bactericidal (kill 99% of bacteria) at 0.1-1 M, and thus are more active than most antibacterial peptides, such as defensins or magainin (1-6, 37), but less active than phospholipase A 2 , which is the most active human bactericidal peptide (1-4, 7).…”

Section: Discussionmentioning

confidence: 99%

“…Besides forming a mechanical barrier, these tissues and their secretions are rich in antimicrobial peptides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), including defensins (1-6), phospholipase A 2 (7), dermicidin (8), cathelicidin (9), RNases (10), and psoriasin (11). Antimicrobial peptides are low molecular weight amphipathic molecules that kill microorganisms by damaging their membranes (1)(2)(3)(4).…”

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confidence: 99%

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Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

Wang

et al. 2006

Journal of Biological Chemistry

198

298

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Skin and mucous membranes come in contact with external environment and protect tissues from infections by producing antimicrobial peptides. We report that human peptidoglycan recognition proteins 3 and 4 (PGLYRP3 and PGLYRP4) are secreted as 89 -115-kDa disulfide-linked homo-and heterodimers and are bactericidal against several pathogenic and nonpathogenic transient, but not normal flora, Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also bacteriostatic toward all other tested bacteria, which include Gram-negative bacteria and normal flora Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also active in vivo and protect mice against experimental lung infection. In contrast to antimicrobial peptides, PGLYRPs kill bacteria by interacting with their cell wall peptidoglycan, rather than permeabilizing their membranes. PGLYRP3 and PGLYRP4 are expressed in the skin, eyes, salivary glands, throat, tongue, esophagus, stomach, and intestine. Thus, we have identified the function of mammalian PGLYRP3 and PGLYRP4, and show that they are a new class of bactericidal and bacteriostatic proteins that have different structures, mechanism of actions, and expression patterns than antimicrobial peptides.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

Wang

et al. 2006

Journal of Biological Chemistry

198

298

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“…Culture of Epithelial Cells-Foreskin-derived keratinocytes, airway epithelial cells, and the A549 lung epithelial cells were prepared and cultured as described previously (17,24). Supernatants of the cells stimulated for 48 h with 10 8 /ml heat-killed (65°C, 45 min) P. aeruginosa (clinical isolate) in fetal calf serum-free medium (bacteria-to-cell ratio of 200:1) were collected for purification of antimicrobial factors.…”

Section: Methodsmentioning

confidence: 99%

Isolation and Characterization of Human μ-Defensin-3, a Novel Human Inducible Peptide Antibiotic

Harder

Bartels

Christophers

et al. 2001

Journal of Biological Chemistry

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The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human ␤-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor ␣ and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.

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“…Defence mechanisms include transepithelial passage of antibodies in the form of IgA (Kelly and Fox, 1979) as part of the adaptive immune response, but depend to a large extent on innate defences. Luminal secretions contain peptides of low molecular weight with antibacterial activity, defensins Valore et al, 1998) and lysosyme (Tauber et al, 1993), as well as compounds such as secretory leucocyte protease inhibitor (SLPI), which have anti-viral, anti-fungal and anti-bacterial activity (Hiemstra et al, 1996;Tomee et al, 1997;Wiedow et al, 1998). SLPI is expressed in human endometrial epithelial cells (King et al, 2000) and may contribute to the luminal defences of the uterus.…”

Section: Epitheliummentioning

confidence: 99%

Cytokine control in human endometrium

Kelly

King²,

Critchley³

2001

Reproduction

211

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Critical reproductive events in endometrium such as menstruation and implantation have an inflammatory character (Finn, 1986). Menstruation and implantation involve both prostaglandins and cytokines and are accompanied by the ingress of leucocytes into the endometrium. Moreover, oedema is characteristic of endometrium both premenstrually and at the time of implantation. Endometrial physiology relating to these events is still poorly understood and this ignorance hinders better medical approaches to major pathologies of menstruation, such as menorrhagia and dysmenorrhoea, and failure of implantation.One of the most revealing studies on the mechanism of menstruation was published 60 years ago by Markee (1940) who transplanted endometrium to the anterior chamber of the monkey eye, where events surrounding menstruation could be observed microscopically. The early events of menstruation involve vasoconstriction of the spiral blood vessels followed by a relaxation of the arterioles and reperfusion of the tissue. Prolonged periods of vasoconstriction that would have induced hypoxia and the inevitable reperfusion injury were also observed. Such periods of vasoconstriction have not been confirmed in women in studies with techniques such as Doppler flow (Gannon et al., 1997) and xenon clearance (Fraser et al., 1987), but such techniques are unlikely to detect highly localized changes. Hypoxia would certainly be a sufficient cause of cytokine release since hypoxia affects the NFκB pathway (Royds et al., 1998) and many genes have hypoxic response elements. Re-exposure to oxygen is likely to be accompanied by an upregulation of cytokine (Karakurum et al., 1994) matrix metalloproteinase (MMP) (Fujimura et al., 1999; Heo et al., 1999) vascular endothelial growth factor (VEGF) (Goldberg and Schneider, 1994;Sharkey et al., 2000) and prostaglandin (Kishimoto et al., 1997) production. However, the events preceding vasoconstriction are less clear. The early events in menstruation are initiated by the withdrawal of the circulating progesterone as a result of the demise of the corpus luteum and are likely to involve cells close to the spiral arterioles where the constriction Cytokines within endometrium participate in both menstruation and implantation but also contribute to the defence mechanisms of the mucosal epithelium. Endometrium is under the control of steroid hormones, particularly progesterone and, thus, control of cytokines by this steroid is important. Although appreciable numbers of progesterone receptors are not found in endometrial leucocytes, progesterone can modulate cytokines by acting on uterine cells expressing the receptor. The NFκB pathway is important in the control of cytokine synthesis and can modulate production of chemokines, matrix metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2. NFκB activity can be inhibited by progesterone by either stimulating synthesis of IκB, the molecule that restrains NFκB in the cytosol, or after binding to the nuclear receptor, competing with NFκB for ...

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Antileukoprotease in Human Skin: An Antibiotic Peptide Constitutively Produced by Keratinocytes

Cited by 158 publications

References 18 publications

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

Isolation and Characterization of Human μ-Defensin-3, a Novel Human Inducible Peptide Antibiotic

Cytokine control in human endometrium

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