Defensins

Federal government websites often end in. The site is secure, defensins.

Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants. Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization. Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions. In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators.

Defensins

Federal government websites often end in. The site is secure. Defensins are a major family of host defense peptides expressed predominantly in neutrophils and epithelial cells. Their broad antimicrobial activities and multifaceted immunomodulatory functions have been extensively studied, cementing their role in innate immunity as a core host-protective component against bacterial, viral and fungal infections. This mini review summarizes the latest findings on the potential pathogenic properties of defensins against the backdrop of their protective roles in antiviral and antibacterial immunity. Further, a succinct description of both tumor-proliferative and -suppressive activities of defensins is also given to highlight their functional and mechanistic complexity in antitumor immunity. The first mammalian defensin, also termed microbicidal cationic protein, was isolated in by Lehrer and colleagues from rabbit lung macrophages 1 , 2. It was not until when the same lab discovered homologous peptides in human neutrophils did Lehrer coin the term defensin 3 , 4 to describe disulfide-stabilized cationic peptides of mammalian origins with broad antimicrobial activity against bacteria, viruses and fungi. HNPs-containing granules normally undergo restricted secretion and are commonly directed for fusion with phagolysosomes, where high concentrations of HNPs directly kill phagocytosed microbes 16 , Upon holocrine secretion and neutrophil infiltration during inflammation, HNPs are released into the extracellular milieu through degranulation of activated neutrophils 17 — HD5 and HD6 are constitutively expressed in and secreted by Paneth cells at the bottom of the small intestinal crypt 12 , 13 , 20 , Since their first discovery in the early s, defensins have been intensively investigated for their broad antimicrobial activities and multifaceted immunomodulatory functions under both physiological and pathogenic conditions. Many excellent reviews have shed light on a multitude of sophisticated molecular and cellular mechanisms by which defensins act against bacteria, viruses and fungi and function as pleiotropic immune effectors in inflammation, development and cancer 5 , 11 , 26 , 29 —

As a library, NLM provides access to scientific literature. Defensins of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. USAdefensins, —

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. What are defensins? What are the structural characteristics of the three vertebrate defensin subclasses?

Enteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant to defensins and even appropriate them to enhance infection despite neutralization of closely related microbes. We therefore hypothesized that defensins impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype of adenovirus in the presence of a human defensin, mutations in the major capsid protein hexon accumulated. In contrast, prior studies identified the vertex proteins as important determinants of defensin antiviral activity. Infection and biochemical assays suggest that a balance between increased cell binding and a downstream block in intracellular trafficking mediated by defensin interactions with all of the major capsid proteins dictates the outcome of infection. These results extensively revise our understanding of the interplay between defensins and non-enveloped viruses. Furthermore, they provide a feasible rationale for defensins shaping viral evolution, resulting in differences in infection phenotypes of closely related viruses. Defensins are potent antimicrobial peptides that are found on human mucosal surfaces and can directly neutralize viruses. They are abundant in the small intestine, which is constantly challenged by ingested viral pathogens.

Defensins

Metrics details. Host defense peptides are a critical component of the innate immune system. Human alpha- and beta-defensin genes are subject to copy number variation CNV and historically the organization of mouse alpha-defensin genes has been poorly defined. Problems were identified with the reference assemblies of all three genomes.

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Volume Paneth cells of the human small intestine express an antimicrobial peptide gene. Harder, J. Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Signaling and Communication in Plants. Economopoulou, M. Schmidtchen A Frick I. Numerous studies have highlighted the therapeutic potential of defensins as a form of treatment for various types of infections. Kumar, P. Their earliest defensin intermediate contained 75 aa and arose by cotranslational removal of the residue signal sequence. Howard O. Molecular Ecology Resources. These studies support the premise that Shigella exploits HD5 for virulence 89 , 91 , thereby explaining not only its extraordinary pathogenicity but also its restricted host selectivity. Electrostatic adsorption to anionic sites on or near the target cell's membrane or for certain defensins to sugars in microbial glycoproteins or LPS result in locally high concentrations that promote defensin aggregation and multimer formation. Colorectal Dis.

Nevertheless, big defensins underwent several independent gene loss events during animal evolution, being only retained in a limited number of phylogenetically distant invertebrates. Here, we explore the evolutionary history of this fascinating HDP family and investigate its patchy distribution in extant metazoans.

FEBS Lett. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? The function of defensins in immune regulation has been discussed above. Zasloff M Epithelial antibiotic induced in states of disease. Madi, A. Mechanism of interaction of different cationic antimicrobial peptides with planar bilayers and with cytoplasmic membrane of Escherichia coli. Enteric defensins: antibiotic peptide components of intestinal host defense. Lange, C. In human breast milk, defensins play a central role in neonate immunity. DNA sequence and analysis of human chromosome 8.