Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2664-2672 ◽  
Author(s):  
Ofer Levy
Keyword(s):  
Host Defense ◽  
Blood Cells ◽  
Antimicrobial Agents ◽  
Severe Infection ◽  
Innate Immune ◽  
Antimicrobial Proteins ◽  
Microbial Invasion ◽  
Immune Mediators ◽  
Rapid Responses ◽  
Proteins And Peptides

Abstract The innate immune system provides rapid and effective host defense against microbial invasion in a manner that is independent of prior exposure to a given pathogen.1 It has long been appreciated that the blood contains important elements that mediate rapid responses to infection. Thus, anatomic compartments with ample blood supply are less frequently infected and recover more readily once infected, whereas regions with poor perfusion are prone to severe infection and may require surgical débridement. Blood-borne innate immune mediators are either carried in circulating blood cells (ie, leukocytes and platelets) or in plasma after release from blood cells or on secretion by the liver.

Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2664-2672 ◽  
Author(s):  
Ofer Levy
Keyword(s):  
Host Defense ◽  
Blood Cells ◽  
Antimicrobial Agents ◽  
Severe Infection ◽  
Innate Immune ◽  
Antimicrobial Proteins ◽  
Microbial Invasion ◽  
Immune Mediators ◽  
Rapid Responses ◽  
Proteins And Peptides

The innate immune system provides rapid and effective host defense against microbial invasion in a manner that is independent of prior exposure to a given pathogen.1 It has long been appreciated that the blood contains important elements that mediate rapid responses to infection. Thus, anatomic compartments with ample blood supply are less frequently infected and recover more readily once infected, whereas regions with poor perfusion are prone to severe infection and may require surgical débridement. Blood-borne innate immune mediators are either carried in circulating blood cells (ie, leukocytes and platelets) or in plasma after release from blood cells or on secretion by the liver.

scholarly journals Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments

2021 ◽  
Vol 12 ◽  
Author(s):  
Rathi Saravanan ◽  
Yeu Khai Choong ◽  
Chun Hwee Lim ◽  
Li Ming Lim ◽  
Jitka Petrlova ◽  
...  
Keyword(s):  
Critical Role ◽  
Innate Immune ◽  
Antimicrobial Proteins ◽  
Cell Free Dna ◽  
Thrombin Cleavage ◽  
Free Dna ◽  
Major Structural Component ◽  
Protease Degradation ◽  
Proteins And Peptides

Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and peptides bound to cfDNA play a critical role in the bactericidal property of NETs. Recent studies have shown that NETs have procoagulant activity, wherein cfDNA triggers thrombin generation through activation of the intrinsic pathway of coagulation. We have recently shown that thrombin binds to NETs in vitro and consequently can alter the proteome of NETs. However, the effect of NETs on thrombin is still unknown. In this study, we report that DNA binding leads to thrombin autolysis and generation of multiple thrombin-derived C-terminal peptides (TCPs) in vitro. Employing a 25-residue prototypic TCP, GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), we show that TCPs bind NETs, thus conferring mutual protection against nuclease and protease degradation. Together, our results demonstrate the complex interplay between coagulation, NET formation, and thrombin cleavage and identify a previously undisclosed mechanism for formation of TCPs.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals Designing New Antibacterial Wound Dressings: Development of a Dual Layer Cotton Material Coated with Poly(Vinyl Alcohol)_Chitosan Nanofibers Incorporating Agrimonia eupatoria L. Extract

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 83
Author(s):  
Cláudia Mouro ◽  
Colum P. Dunne ◽  
Isabel C. Gouveia
Keyword(s):  
Composite Material ◽  
Vinyl Alcohol ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Coating Layer ◽  
Wound Dressings ◽  
Poly Vinyl Alcohol ◽  
Microbial Invasion ◽  
Layer Composite ◽  
Medicinal Plant Extracts

Wounds display particular vulnerability to microbial invasion and infections by pathogenic bacteria. Therefore, to reduce the risk of wound infections, researchers have expended considerable energy on developing advanced therapeutic dressings, such as electrospun membranes containing antimicrobial agents. Among the most used antimicrobial agents, medicinal plant extracts demonstrate considerable potential for clinical use, due primarily to their efficacy allied to relatively low incidence of adverse side-effects. In this context, the present work aimed to develop a unique dual-layer composite material with enhanced antibacterial activity derived from a coating layer of Poly(vinyl alcohol) (PVA) and Chitosan (CS) containing Agrimonia eupatoria L. (AG). This novel material has properties that facilitate it being electrospun above a conventional cotton gauze bandage pre-treated with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical (TEMPO). The produced dual-layer composite material demonstrated features attractive in production of wound dressings, specifically, wettability, porosity, and swelling capacity. Moreover, antibacterial assays showed that AG-incorporated into PVA_CS’s coating layer could effectively inhibit Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) growth. Equally important, the cytotoxic profile of the dual-layer material in normal human dermal fibroblast (NHDF) cells demonstrated biocompatibility. In summary, these data provide initial confidence that the TEMPO-oxidized cotton/PVA_CS dressing material containing AG extract demonstrates adequate mechanical attributes for use as a wound dressing and represents a promising approach to prevention of bacterial wound contamination.

scholarly journals Contributions of Electron Microscopy to Understand Secretion of Immune Mediators by Human Eosinophils

2010 ◽  
Vol 16 (6) ◽  
pp. 653-660 ◽  
Author(s):  
Rossana C.N. Melo ◽  
Ann M. Dvorak ◽  
Peter F. Weller
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
Cell Secretion ◽  
The Past ◽  
Functional Capabilities ◽  
Immune Mediators ◽  
Transmission Electron

AbstractMechanisms governing secretion of proteins underlie the biologic activities and functions of human eosinophils, leukocytes of the innate immune system, involved in allergic, inflammatory, and immunoregulatory responses. In response to varied stimuli, eosinophils are recruited from the circulation into inflammatory foci, where they modulate immune responses through the release of granule-derived products. Transmission electron microscopy (TEM) is the only technique that can clearly identify and distinguish between different modes of cell secretion. In this review, we highlight the advances in understanding mechanisms of eosinophil secretion, based on TEM findings, that have been made over the past years and that have provided unprecedented insights into the functional capabilities of these cells.

Houttuynia cordatamodulates oral innate immune mediators: potential role of herbal plant on oral health

Oral Diseases ◽  
2015 ◽  
Vol 21 (4) ◽  
pp. 512-518 ◽  
Author(s):  
S Satthakarn ◽  
WO Chung ◽  
A Promsong ◽  
W Nittayananta
Keyword(s):  
Oral Health ◽  
Potential Role ◽  
Innate Immune ◽  
Immune Mediators ◽  
Herbal Plant

DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia

2021 ◽  
Vol 13 (616) ◽  
Author(s):  
L. K. Metthew Lam ◽  
Sophia Murphy ◽  
Dimitra Kokkinaki ◽  
Alessandro Venosa ◽  
Scott Sherrill-Mix ◽  
...  
Keyword(s):  
Dna Binding ◽  
Red Blood Cells ◽  
Immune Activation ◽  
Blood Cells ◽  
Innate Immune ◽  
Innate Immune Activation

scholarly journals Lipid droplets and the host–pathogen dynamic: FATal attraction?

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Marta Bosch ◽  
Matthew J. Sweet ◽  
Robert G. Parton ◽  
Albert Pol
Keyword(s):  
Innate Immunity ◽  
Lipid Droplets ◽  
Innate Immune ◽  
Metabolic Energy ◽  
Eukaryotic Cells ◽  
Bioactive Lipids ◽  
Front Line ◽  
Antimicrobial Proteins ◽  
Current State ◽  
Fatal Attraction

In the ongoing conflict between eukaryotic cells and pathogens, lipid droplets (LDs) emerge as a choke point in the battle for nutrients. While many pathogens seek the lipids stored in LDs to fuel an expensive lifestyle, innate immunity rewires lipid metabolism and weaponizes LDs to defend cells and animals. Viruses, bacteria, and parasites directly and remotely manipulate LDs to obtain substrates for metabolic energy, replication compartments, assembly platforms, membrane blocks, and tools for host colonization and/or evasion such as anti-inflammatory mediators, lipoviroparticles, and even exosomes. Host LDs counterattack such advances by synthesizing bioactive lipids and toxic nucleotides, organizing immune signaling platforms, and recruiting a plethora of antimicrobial proteins to provide a front-line defense against the invader. Here, we review the current state of this conflict. We will discuss why, when, and how LDs efficiently coordinate and precisely execute a plethora of immune defenses. In the age of antimicrobial resistance and viral pandemics, understanding innate immune strategies developed by eukaryotic cells to fight and defeat dangerous microorganisms may inform future anti-infective strategies.

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