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Richard L. Gallo - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Peptides in human skin disease
European journal of dermatology : EJD, 2007Co-Authors: Kenshi Yamasaki, Richard L. GalloAbstract:The skin continuously encounters microbial pathogens. To defend against this, cells of the epidermis and dermis have evolved several innate strategies to prevent infection. Antimicrobial Peptides are one of the primary mechanisms used by the skin in the early stages of immune defense. In general, Antimicrobial Peptides have broad antibacterial activity against gram-positive and negative bacteria and also show antifungal and antiviral activity. The Antimicrobial activity of most Peptides occurs as a result of unique structural characteristics that enable them to disrupt the microbial membrane while leaving human cell membranes intact. However, Antimicrobial Peptides also act on host cells to stimulate cytokine production, cell migration, proliferation, maturation, and extracellular matrix synthesis. The production by human skin of Antimicrobial Peptides such as defensins and cathelicidins occurs constitutively but also greatly increases after infection, inflammation or injury. Some skin diseases show altered expression of Antimicrobial Peptides, partially explaining the pathophysiology of these diseases. Thus, current research suggests that understanding how Antimicrobial Peptides modify susceptibility to microbes, influence skin inflammation, and modify wound healing, provides greater insight into the pathophysiology of skin disorders and offers new therapeutic opportunities.
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cutaneous defense mechanisms by Antimicrobial Peptides
Journal of Investigative Dermatology, 2005Co-Authors: Marissa H Braff, Antoanella Bardan, Victor Nizet, Richard L. GalloAbstract:The skin actively contributes to host defense by mounting an innate immune response that includes the production of Antimicrobial Peptides. These Peptides, which include but are not limited to the cathelicidin and defensin gene families, provide rapid, broad-spectrum defense against infection by acting as natural antibiotics and by participating in host cell processes involved in immune defense. This review discusses the biology and clinical relevance of Antimicrobial Peptides expressed in the skin. The importance of the epithelial contribution to host immunity is evident, as alterations in Antimicrobial peptide expression have been associated with various pathologic processes.
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Antimicrobial Peptides in human health and disease
2005Co-Authors: Richard L. GalloAbstract:Introduction. General Concepts of Antimicrobial Peptides, Past and Future. Section 1. Select Diverse Peptides with Antimicrobial Action in Humans. 1. The Role of Cathelicidins in the Innate Host Defences of Mammals. 2. The Role of Alpha and Beta Defensins in Human Defense. 3. Granulysin. 4. Hepcidin. Section 2 Tissues and their use of Antimicrobial Peptides. 5. Antimicrobial Peptides in Human Blood. 6. The Role of Paneth Cell a-Defensins in Enteric Innate Immunity. 7. Lung. 8. Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease. 9. Natural Antimicrobial Peptides: A Barrier against Human Skin Infection. Section 3 Clinical Concepts. 10. Antimicrobial Peptide Resistance in Human Bacterial Pathogens. 11. A Pediatric Perspective on Antimicrobial Proteins and Peptides: Expression, Function, and Clinical Relevance. 12. Therapeutic Applications of Innate Immunity Peptides.
Steven W. Taylor - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Peptides from Marine Invertebrates
Antimicrobial agents and chemotherapy, 2004Co-Authors: J. Andy Tincu, Steven W. TaylorAbstract:Marine invertebrates lack an acquired, memory-type immunity based on T-lymphocyte subsets and clonally derived immunoglobulins (72). This differs from the vertebrate immune system, which is characterized by somatic gene rearrangement, clonal selection, and expansion and a discriminative ability that includes lymphocytes, among other factors, which impart specificity and memory (71). Marine invertebrates rely solely on innate immune mechanisms that include both humoral and cellular responses. Humoral immunity in marine invertebrates is characterized by Antimicrobial agents present in the blood cells and plasma (92), along with reactions such as hemolymph coagulation or melanization (79, 85). Cellular immunity in marine invertebrates is based on cell defense reactions, including encapsulation, nodule formation, and phagocytosis (92). The cellular component of marine invertebrate immunity is mediated by hemocytes, motile cells that phagocytize microbes and secrete soluble Antimicrobial and cytotoxic substances into the hemolymph (53). This differs from insects, especially Drosophila melanogaster, which rely largely on the challenge-induced synthesis of Antimicrobial Peptides by the fat body (30, 88) and use exclusion, via a tough exoskeleton, as their major Antimicrobial defense. The circulating hemolymph in marine invertebrates contains biologically active substances such as complement, lectins, clotting factors, and Antimicrobial Peptides (57). All of these factors contribute to a self-defense system in marine invertebrates against invading microorganisms, which can number up to 106 bacteria/ml and 109 virus/ml of seawater (2). The survival of marine invertebrates in this environment suggests that their innate immune system is effective and robust (52). Antimicrobial Peptides are a major component of the innate immune defense system in marine invertebrates. They are defined as molecules less than 10 kDa in mass which show Antimicrobial properties (12) and provide an immediate and rapid response to invading microorganisms (8). The major classes of Antimicrobial Peptides include (i) α-helices, (ii) β-sheet and small proteins, (iii) Peptides with thio-ether rings, (iv) Peptides with an overrepresentation of one or two amino acids, (v) lipoPeptides, and (vi) macrocyclic cystine knot Peptides (24). There is evidence that Antimicrobial Peptides are widespread in invertebrates (15), especially in tissues such as the gut and respiratory organs in marine invertebrates, where exposure to pathogenic microorganisms is likely. In spite of variations in structure and size, the majority of Antimicrobial Peptides are amphiphilic, displaying both hydrophilic and hydrophobic surfaces. These Peptides generally act by forming pores in microbial membranes or otherwise disrupting membrane integrity (82), which is facilitated by their amphiphilic structure. This mode of action is unlikely to lead to the development of resistance (9, 58), although it must be noted that this presumption is debatable (10). Recently, cationic Antimicrobial Peptides have been reported to be involved in many aspects of innate host defenses, associated with processes such as acute inflammation (25). The value of Antimicrobial Peptides in innate immunity lies in their ability to function without either high specificity or memory, and their small size makes them easy to synthesize (72). In addition, many antibacterial Peptides show remarkable specificity for prokaryotes with low toxicity for eukaryotic cells (97). This is a characteristic that has favored their investigation and exploitation as potential new antibiotics (97). The recent appearance of a growing number of bacteria resistant to conventional antibiotics has become a serious medical problem. To overcome this resistance, the development of antibiotics with novel mechanisms of action is a pressing issue (48). Endogenous Antimicrobial Peptides are exciting candidates as new antibacterial agents due to their broad Antimicrobial spectra, highly selective toxicities, and the difficulty for bacteria to develop resistance to these Peptides (11, 26, 47). The ocean covers 71% of the surface of the earth and contains approximately half of the total global biodiversity, with estimates ranging between 3 and 500 × 106 different species (28). Marine macrofauna alone comprise 0.5 to 10 × 106 species (23). Therefore, the marine environment, especially marine invertebrates that rely solely on innate immune mechanisms for host defense, is a spectacular resource for the development of new Antimicrobial compounds. This minireview will encompass what is known about gene-encoded Antimicrobial Peptides from marine invertebrates, covering the phyla Arthropoda, Chordata, and Mollusca (Table (Table11). TABLE 1. Antimicrobial Peptides from marine invertebrates
Tomas Ganz - One of the best experts on this subject based on the ideXlab platform.
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Defensins and Other Antimicrobial Peptides: Innate Defense of Mucosal Surfaces
Colonization of Mucosal Surfaces, 2014Co-Authors: Alexander M. Cole, Tomas GanzAbstract:This chapter provides an in-depth account of defensins, and ties together the roles of other Antimicrobial Peptides and proteins that together contribute to mucosal innate host defense. While the focus is on defensins and Antimicrobial Peptides from humans, Peptides from other species are also included where appropriate. The structural and functional relationships between these three classes of alpha-defensins, beta-defensins, theta-defensins are discussed in this chapter. The antibacterial and antifungal activities of the resulting retrocyclin were modest and were similar to those of synthetic and native rhesus theta-defensins. The noticeable salt sensitivity of ELR- CXC chemokines was similar to that of defensins and many other Antimicrobial Peptides. High concentrations of alpha-defensins are frequently observed in chronically inflamed tissues. Certain factors within airway fluid, including electrolytes and anionic macromolecules, decrease the activity of many Antimicrobial Peptides, including defensins. Even though the processing of human neutrophil alpha-defensins occurs during neutrophil maturation prior to cellular release from the bone marrow, matrilysin may participate in the activation of beta-defensins or other Antimicrobial Peptides in the human airways. Defensins and other Antimicrobial Peptides and proteins coat mucosal surfaces and are among the primary early mediators of host defense against colonization and tissue invasion by pathogenic microbes. In vitro and in vivo studies indicate that most Antimicrobial Peptides probably act as endogenous antibiotics.
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Defensins: Antimicrobial Peptides of vertebrates.
Comptes rendus biologies, 2004Co-Authors: Tomas GanzAbstract:Abstract This review, based on my presentation at the French Academy of Sciences on May 19, 2003, describes recent progress in the study of Antimicrobial Peptides, mediators of innate immunity in plants and animals. The main focus is on vertebrate defensins, a family of cysteine-rich Antimicrobial Peptides abundantly represented in human cells and tissues. To cite this article: T. Ganz, C. R. Biologies 327 (2004).
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Human Antimicrobial Peptides: analysis and application.
BioTechniques, 2000Co-Authors: Alexander M. Cole, Tomas GanzAbstract:Antimicrobial Peptides are innate host defense molecules that have a direct effect on bacteria, fungi and enveloped viruses. They are found in evolutionarily diverse species ranging from prokaryotes and plants to invertebrate and vertebrate animals. Humans express several families of Antimicrobial Peptides in myeloid cells and on various epithelial surfaces where they are poised to defend against pathogens. Recently, Antimicrobial Peptides from animals and plants have served as templates for the design of new therapeutic antibiotics. This review provides an introduction to the biology of human Antimicrobial Peptides, followed by a more detailed discussion of their isolation from tissues and biological fluids, their purification by gel electrophoresis and chromatography and assays of their Antimicrobial activities.
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Antimicrobial Peptides OF VERTEBRATES
Current opinion in immunology, 1998Co-Authors: Tomas Ganz, Robert I. LehrerAbstract:The past year brought several discoveries that focused attention on Antimicrobial Peptides on epithelial surfaces. The malfunction of these substances was implicated as a cause of airway infections in cystic fibrosis. Other highlights included new insights into the relative selectivity of Antimicrobial Peptides for microbial membranes, their primary site of action.
Alexander M. Cole - One of the best experts on this subject based on the ideXlab platform.
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Defensins and Other Antimicrobial Peptides: Innate Defense of Mucosal Surfaces
Colonization of Mucosal Surfaces, 2014Co-Authors: Alexander M. Cole, Tomas GanzAbstract:This chapter provides an in-depth account of defensins, and ties together the roles of other Antimicrobial Peptides and proteins that together contribute to mucosal innate host defense. While the focus is on defensins and Antimicrobial Peptides from humans, Peptides from other species are also included where appropriate. The structural and functional relationships between these three classes of alpha-defensins, beta-defensins, theta-defensins are discussed in this chapter. The antibacterial and antifungal activities of the resulting retrocyclin were modest and were similar to those of synthetic and native rhesus theta-defensins. The noticeable salt sensitivity of ELR- CXC chemokines was similar to that of defensins and many other Antimicrobial Peptides. High concentrations of alpha-defensins are frequently observed in chronically inflamed tissues. Certain factors within airway fluid, including electrolytes and anionic macromolecules, decrease the activity of many Antimicrobial Peptides, including defensins. Even though the processing of human neutrophil alpha-defensins occurs during neutrophil maturation prior to cellular release from the bone marrow, matrilysin may participate in the activation of beta-defensins or other Antimicrobial Peptides in the human airways. Defensins and other Antimicrobial Peptides and proteins coat mucosal surfaces and are among the primary early mediators of host defense against colonization and tissue invasion by pathogenic microbes. In vitro and in vivo studies indicate that most Antimicrobial Peptides probably act as endogenous antibiotics.
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Minidefensins and other Antimicrobial Peptides: candidate anti-HIV microbicides
Expert opinion on therapeutic targets, 2003Co-Authors: Alexander M. ColeAbstract:Antimicrobial Peptides have long been presumed to act as effector molecules of innate immunity. However, direct evidence that Antimicrobial Peptides have central roles in host defence has only recently become available. An overview of the types and characteristics of endogenous human Antimicrobial Peptides and proteins is presented, with particular emphasis on Peptides that are active against HIV. These antiviral Peptides are discussed in the context of utilising natural Peptides for the design of effective topical microbicides for the treatment of sexually transmitted infections (STIs). Several Antimicrobial Peptides, termed minidefensins, are potently active against HIV, and bear structural similarity to their larger defensin cousins. Strategies to develop potent peptide antibiotics based on defensin and minidefensin templates are promising in the development of antiviral therapeutics and preventatives.
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Human Antimicrobial Peptides: analysis and application.
BioTechniques, 2000Co-Authors: Alexander M. Cole, Tomas GanzAbstract:Antimicrobial Peptides are innate host defense molecules that have a direct effect on bacteria, fungi and enveloped viruses. They are found in evolutionarily diverse species ranging from prokaryotes and plants to invertebrate and vertebrate animals. Humans express several families of Antimicrobial Peptides in myeloid cells and on various epithelial surfaces where they are poised to defend against pathogens. Recently, Antimicrobial Peptides from animals and plants have served as templates for the design of new therapeutic antibiotics. This review provides an introduction to the biology of human Antimicrobial Peptides, followed by a more detailed discussion of their isolation from tissues and biological fluids, their purification by gel electrophoresis and chromatography and assays of their Antimicrobial activities.
J. Andy Tincu - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Peptides from Marine Invertebrates
Antimicrobial agents and chemotherapy, 2004Co-Authors: J. Andy Tincu, Steven W. TaylorAbstract:Marine invertebrates lack an acquired, memory-type immunity based on T-lymphocyte subsets and clonally derived immunoglobulins (72). This differs from the vertebrate immune system, which is characterized by somatic gene rearrangement, clonal selection, and expansion and a discriminative ability that includes lymphocytes, among other factors, which impart specificity and memory (71). Marine invertebrates rely solely on innate immune mechanisms that include both humoral and cellular responses. Humoral immunity in marine invertebrates is characterized by Antimicrobial agents present in the blood cells and plasma (92), along with reactions such as hemolymph coagulation or melanization (79, 85). Cellular immunity in marine invertebrates is based on cell defense reactions, including encapsulation, nodule formation, and phagocytosis (92). The cellular component of marine invertebrate immunity is mediated by hemocytes, motile cells that phagocytize microbes and secrete soluble Antimicrobial and cytotoxic substances into the hemolymph (53). This differs from insects, especially Drosophila melanogaster, which rely largely on the challenge-induced synthesis of Antimicrobial Peptides by the fat body (30, 88) and use exclusion, via a tough exoskeleton, as their major Antimicrobial defense. The circulating hemolymph in marine invertebrates contains biologically active substances such as complement, lectins, clotting factors, and Antimicrobial Peptides (57). All of these factors contribute to a self-defense system in marine invertebrates against invading microorganisms, which can number up to 106 bacteria/ml and 109 virus/ml of seawater (2). The survival of marine invertebrates in this environment suggests that their innate immune system is effective and robust (52). Antimicrobial Peptides are a major component of the innate immune defense system in marine invertebrates. They are defined as molecules less than 10 kDa in mass which show Antimicrobial properties (12) and provide an immediate and rapid response to invading microorganisms (8). The major classes of Antimicrobial Peptides include (i) α-helices, (ii) β-sheet and small proteins, (iii) Peptides with thio-ether rings, (iv) Peptides with an overrepresentation of one or two amino acids, (v) lipoPeptides, and (vi) macrocyclic cystine knot Peptides (24). There is evidence that Antimicrobial Peptides are widespread in invertebrates (15), especially in tissues such as the gut and respiratory organs in marine invertebrates, where exposure to pathogenic microorganisms is likely. In spite of variations in structure and size, the majority of Antimicrobial Peptides are amphiphilic, displaying both hydrophilic and hydrophobic surfaces. These Peptides generally act by forming pores in microbial membranes or otherwise disrupting membrane integrity (82), which is facilitated by their amphiphilic structure. This mode of action is unlikely to lead to the development of resistance (9, 58), although it must be noted that this presumption is debatable (10). Recently, cationic Antimicrobial Peptides have been reported to be involved in many aspects of innate host defenses, associated with processes such as acute inflammation (25). The value of Antimicrobial Peptides in innate immunity lies in their ability to function without either high specificity or memory, and their small size makes them easy to synthesize (72). In addition, many antibacterial Peptides show remarkable specificity for prokaryotes with low toxicity for eukaryotic cells (97). This is a characteristic that has favored their investigation and exploitation as potential new antibiotics (97). The recent appearance of a growing number of bacteria resistant to conventional antibiotics has become a serious medical problem. To overcome this resistance, the development of antibiotics with novel mechanisms of action is a pressing issue (48). Endogenous Antimicrobial Peptides are exciting candidates as new antibacterial agents due to their broad Antimicrobial spectra, highly selective toxicities, and the difficulty for bacteria to develop resistance to these Peptides (11, 26, 47). The ocean covers 71% of the surface of the earth and contains approximately half of the total global biodiversity, with estimates ranging between 3 and 500 × 106 different species (28). Marine macrofauna alone comprise 0.5 to 10 × 106 species (23). Therefore, the marine environment, especially marine invertebrates that rely solely on innate immune mechanisms for host defense, is a spectacular resource for the development of new Antimicrobial compounds. This minireview will encompass what is known about gene-encoded Antimicrobial Peptides from marine invertebrates, covering the phyla Arthropoda, Chordata, and Mollusca (Table (Table11). TABLE 1. Antimicrobial Peptides from marine invertebrates