scholarly journals β2 Integrin Regulation of Neutrophil Functional Plasticity and Fate in the Resolution of Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Meriem Sekheri ◽  
Amira Othman ◽  
János G. Filep
Keyword(s):  
Tissue Injury ◽  
Resolution Of Inflammation ◽  
Cellular Defense ◽  
Adaptive Immune ◽  
The Past ◽  
Extracellular Traps ◽  
Antimicrobial Function ◽  
Complement Receptor 3 ◽  
Integrin Regulation ◽  
Functional Versatility

Neutrophils act as the first line of cellular defense against invading pathogens or tissue injury. Their rapid recruitment into inflamed tissues is critical for the elimination of invading microorganisms and tissue repair, but is also capable of inflicting damage to neighboring tissues. The β2 integrins and Mac-1 (CD11b/CD18, αMβ2 or complement receptor 3) in particular, are best known for mediating neutrophil adhesion and transmigration across the endothelium and phagocytosis of microbes. However, Mac-1 has a broad ligand recognition property that contributes to the functional versatility of the neutrophil population far beyond their antimicrobial function. Accumulating evidence over the past decade has demonstrated roles for Mac-1 ligands in regulating reverse neutrophil transmigration, lifespan, phagocytosis-induced cell death, release of neutrophil extracellular traps and efferocytosis, hence extending the traditional β2 integrin repertoire in shaping innate and adaptive immune responses. Understanding the functions of β2 integrins may partly explain neutrophil heterogeneity and may be instrumental to develop novel therapies specifically targeting Mac-1-mediated pro-resolution actions without compromising immunity. Thus, this review details novel insights on outside-in signaling through β2 integrins and neutrophil functional heterogeneity pertinent to the resolution of inflammation.

Energy Sources for the Surgical Treatment of Atrial Fibrillation

2019 ◽  
Vol 14 (6) ◽  
pp. 503-508
Author(s):  
Robert M. MacGregor ◽  
Spencer J. Melby ◽  
Richard B. Schuessler ◽  
Ralph J. Damiano
Keyword(s):  
Atrial Fibrillation ◽  
Surgical Treatment ◽  
Tissue Injury ◽  
Surgical Techniques ◽  
Maze Procedure ◽  
Energy Sources ◽  
Surgical Approaches ◽  
Surgical Ablation ◽  
The Past ◽  
Minimally Invasive Surgical

The surgical treatment of atrial fibrillation has evolved over the past 2 decades due to the advent of ablation technology, and the introduction of less invasive surgical approaches. Current devices produce ablation lines that aim to replace the incisions of traditional surgical ablation strategies, such as the Cox-Maze procedure. This has helped to simplify and shorten surgical ablation procedures and has allowed for the development of minimally invasive surgical techniques. This review discusses surgical ablation energy sources and devices, providing background on device characteristics, mechanism of tissue injury, and success in creating transmural lesions.

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

2014 ◽  
Vol 307 (7) ◽  
pp. L586-L596 ◽  
Author(s):  
Lingtao Luo ◽  
Su Zhang ◽  
Yongzhi Wang ◽  
Milladur Rahman ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Lung Injury ◽  
Peritoneal Cavity ◽  
Tissue Injury ◽  
Cecal Ligation ◽  
Neutrophil Extracellular Traps ◽  
Abdominal Sepsis ◽  
Extracellular Dna ◽  
Extracellular Traps ◽  
Proinflammatory Role

Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with recombinant human (rh)DNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green, and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity, and lung. Blood, peritoneal fluid, and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury, as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in plasma, peritoneal cavity, and lung. Administration of rhDNAse not only eliminated NET formation in plasma, peritoneal cavity, and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6, and high-mobility group box 1 (HMGB1) in plasma, as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α, and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of proinflammatory compounds in abdominal sepsis. Thus we conclude that NETs exert a proinflammatory role in septic lung injury.

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

Blood ◽  
2016 ◽  
Vol 127 (18) ◽  
pp. 2173-2181 ◽  
Author(s):  
Carlos Silvestre-Roig ◽  
Andres Hidalgo ◽  
Oliver Soehnlein
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Innate Immune ◽  
First Line ◽  
Adaptive Immune ◽  
Differentiated Cells ◽  
Short Lifespan ◽  
Mediators Of Inflammation ◽  
Functional Versatility ◽  
Homogenous Population

Abstract Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease.

scholarly journals Cancer Therapy Targeting CD47/SIRPα

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6229
Author(s):  
Nazli Dizman ◽  
Elizabeth I. Buchbinder
Keyword(s):  
Immune Responses ◽  
Clinical Evidence ◽  
Immune Escape ◽  
Cell Surface Molecule ◽  
Adaptive Immune ◽  
The Past ◽  
A Cell ◽  
Cancer Types ◽  
Early Phase Clinical Trials ◽  
Immune Checkpoint Blockers

In the past decade, the field of cancer immunotherapy has rapidly advanced, establishing a crucial role for immune checkpoint blockers in the treatment of a variety of cancer types. In parallel with these remarkable clinical developments, further efforts have focused on ways of unleashing adaptive immune responses against cancer. CD47, a cell surface molecule overexpressed by several cancer types that facilitates immune escape from macrophages, dendritic cells and natural killer cells, and its ligand SIRPα, have emerged as potential therapeutic targets. A number of agents directed to CD47/SIRPα have been developed and demonstrated preclinical activity. Early phase clinical trials are investigating CD47/SIRPα directed agents with available data, suggesting safety and preliminary activity. Herein, we provide an overview of the mechanistic rationale of targeting CD47/SIRPα axis and associated clinical evidence.

scholarly journals Immune System Disequilibrium—Neutrophils, Their Extracellular Traps, and COVID-19-Induced Sepsis

2021 ◽  
Vol 8 ◽  
Author(s):  
Colm Keane ◽  
Matthew Coalter ◽  
Ignacio Martin-Loeches
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Organ Injury ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Adaptive Immune ◽  
Extracellular Traps ◽  
Adaptive Immune Cells ◽  
Induced Apoptosis

Equilibrium within the immune system can often determine the fate of its host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Immune dysregulation remains one of the main pathophysiological components of SARS-CoV-2-associated organ injury, with over-activation of the innate immune system, and induced apoptosis of adaptive immune cells. Here, we provide an overview of the innate immune system, both in general and relating to COVID-19. We specifically discuss “NETosis,” the process of neutrophil release of their extracellular traps, which may be a more recently described form of cell death that is different from apoptosis, and how this may propagate organ dysfunction in COVID-19. We complete this review by discussing Stem Cell Therapies in COVID-19 and emerging COVID-19 phenotypes, which may allow for more targeted therapy in the future. Finally, we consider the array of potential therapeutic targets in COVID-19, and associated therapeutics.

scholarly journals Abdominal Aortic Aneurysm: Roles of Inflammatory Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Yuan ◽  
Yi Lu ◽  
Jia Wei ◽  
Jiaqi Wu ◽  
Jin Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Aortic Aneurysms ◽  
Interaction Networks ◽  
Pharmacological Interventions ◽  
The Past ◽  
Extracellular Traps ◽  
Abdominal Aortic ◽  
Direct Cell ◽  
New Strategies

Abdominal aortic aneurysms (AAAs) are local dilations of infrarenal segment of aortas. Molecular mechanisms underlying the pathogenesis of AAA remain not fully clear. However, inflammation has been considered as a central player in the development of AAA. In the past few decades, studies demonstrated a host of inflammatory cells, including T cells, macrophages, dendritic cells, neutrophils, B cells, and mast cells, etc. infiltrating into aortic walls, which implicated their crucial roles. In addition to direct cell contacts and cytokine or protease secretions, special structures like inflammasomes and neutrophil extracellular traps have been investigated to explore their functions in aneurysm formation. The above-mentioned inflammatory cells and associated structures may initiate and promote AAA expansion. Understanding their impacts and interaction networks formation is meaningful to develop new strategies of screening and pharmacological interventions for AAA. In this review, we aim to discuss the roles and mechanisms of these inflammatory cells in AAA pathogenesis.

scholarly journals CRISPR systems: what’s new, where next?

2021 ◽  
Author(s):  
Ashley Parkes ◽  
Fiona Kemm ◽  
Liu He ◽  
Tom Killelea
Keyword(s):  
Dna Repair ◽  
Immune System ◽  
Genetic Engineering ◽  
Gene Editing ◽  
Adaptive Immune System ◽  
Feature Article ◽  
Adaptive Immune ◽  
The Past ◽  
Domains Of Life ◽  
Made In

The genetic signature of natural CRISPR-Cas systems were first noted in a 1989 publication and were characterized in detail from 2002 to 2007, culminating in the first report of a prokaryotic adaptive immune system. Since then, CRISPR-Cas enzymes have been adapted into molecular biology tools that have transformed genetic engineering across domains of life. In this feature article, we describe origins, uses and futures of CRISPR-Cas enzymes in genetic engineering: we highlight advances made in the past 10 years. Central to these advances is appreciation of interplay between CRISPR engineering and DNA repair. We highlight how this relationship has been manipulated to create further advances in the development of gene editing.

scholarly journals The CRISPR-Cas Mechanism for Adaptive Immunity and Alternate Bacterial Functions Fuels Diverse Biotechnologies

2021 ◽  
Vol 10 ◽  
Author(s):  
Sydney Newsom ◽  
Hari Priya Parameshwaran ◽  
Lindsie Martin ◽  
Rakhi Rajan
Keyword(s):  
Biofilm Formation ◽  
Specific Binding ◽  
Genome Medicine ◽  
Adaptive Immune ◽  
The Past ◽  
Dna Motif ◽  
Protospacer Adjacent Motif ◽  
Target Dna ◽  
And Control ◽  
Cas Proteins

Bacterial and archaeal CRISPR-Cas systems offer adaptive immune protection against foreign mobile genetic elements (MGEs). This function is regulated by sequence specific binding of CRISPR RNA (crRNA) to target DNA/RNA, with an additional requirement of a flanking DNA motif called the protospacer adjacent motif (PAM) in certain CRISPR systems. In this review, we discuss how the same fundamental mechanism of RNA-DNA and/or RNA-RNA complementarity is utilized by bacteria to regulate two distinct functions: to ward off intruding genetic materials and to modulate diverse physiological functions. The best documented examples of alternate functions are bacterial virulence, biofilm formation, adherence, programmed cell death, and quorum sensing. While extensive complementarity between the crRNA and the targeted DNA and/or RNA seems to constitute an efficient phage protection system, partial complementarity seems to be the key for several of the characterized alternate functions. Cas proteins are also involved in sequence-specific and non-specific RNA cleavage and control of transcriptional regulator expression, the mechanisms of which are still elusive. Over the past decade, the mechanisms of RNA-guided targeting and auxiliary functions of several Cas proteins have been transformed into powerful gene editing and biotechnological tools. We provide a synopsis of CRISPR technologies in this review. Even with the abundant mechanistic insights and biotechnology tools that are currently available, the discovery of new and diverse CRISPR types holds promise for future technological innovations, which will pave the way for precision genome medicine.

scholarly journals The Role of Creatine in the Development and Activation of Immune Responses

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 751
Author(s):  
Eric C. Bredahl ◽  
Joan M. Eckerson ◽  
Steven M. Tracy ◽  
Thomas L. McDonald ◽  
Kristen M. Drescher
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Health Care Professionals ◽  
Elite Athletes ◽  
Nutritional Supplements ◽  
The Elderly ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Past

The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.

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