scholarly journals Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mahin Behzadi Fard ◽  
Samaneh Behzadi Fard ◽  
Shahin Ramazi ◽  
Amir Atashi ◽  
Zahra Eslamifar
Keyword(s):  
Platelet Activation ◽  
Coronary Thrombosis ◽  
Oxygen Demand ◽  
Main Body ◽  
Lectin Receptor ◽  
Multiple Receptors ◽  
Viral Therapy ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Background Thrombosis plays an important role in the Coronavrus Disease 2019 (COVID-19) infection-related complications such as acute respiratory distress syndrome and myocardial infarction. Multiple factors such as oxygen demand injuries, endothelial cells injury related to infection, and plaque formation. Main body Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases. Platelets contain multiple receptors that interact with specific ligands. Pathogen’s receptors such as Toll-like receptors (TLRs), NOD-like receptor, C-type lectin receptor family, glycoprotein (GP) such as GPαIIbβ3 and GPIbα which allow pathogens to interact with platelets. Platelet TLRs and NOD2 are involved in platelet activation and thrombosis. Accordingly, TLRs are critical receptors that could recognize various endogenous damage-associated molecular patterns and exogenous pathogen-associated molecular patterns (PAMPs). TLRs are considered as important components in the activation of innate immunity response against pathogenic and non-pathogenic components like damaged tissues. TLRs-1,-2,-4,-6,-7 expression on or within platelets has been reported previously. Various PAMPs were indicated to be capable of binding to platelet-TLRs and inducing both the activation and promotion of downstream proinflammatory signaling cascade. Conclusion It is possible that the increased TLRs expression and TLR-mediated platelets activation during COVID-19 may enhance vascular and coronary thrombosis. It may be hypothesized using TLRs antagonist and monoclonal antibody against P-selectin, as the marker of leukocyte recruitment and platelet activation, besides viral therapy provide therapeutic advances in fighting against the thrombosis related complications in COVID-19.

scholarly journals The role of leukocytes in thrombosis

Blood ◽  
2016 ◽  
Vol 128 (6) ◽  
pp. 753-762 ◽  
Author(s):  
Laura L. Swystun ◽  
Patricia C. Liaw
Keyword(s):  
Platelet Activation ◽  
Thrombus Formation ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Immune Functions ◽  
Hemostatic System ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
New Evidence

AbstractIn recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage-associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways. Leukocyte-released procoagulant mediators increase systemic thrombogenicity, and leukocytes are actively recruited to the site of thrombus formation through interactions with platelets and endothelial cell adhesion molecules. Additionally, phagocytic leukocytes are involved in fibrinolysis and thrombus resolution, and can regulate clearance of platelets and coagulation factors. Dysregulated activation of leukocyte innate immune functions thus plays a role in pathological thrombus formation. Modulation of the interactions between leukocytes or leukocyte-derived procoagulant materials and the traditional hemostatic system is an attractive target for the development of novel antithrombotic strategies.

scholarly journals Toll-Like Receptors and Myocardial Inflammation

2011 ◽  
Vol 2011 ◽  
pp. 1-21 ◽  
Author(s):  
Yan Feng ◽  
Wei Chao
Keyword(s):  
Animal Studies ◽  
Myocardial Injury ◽  
Myocardial Inflammation ◽  
Septic Cardiomyopathy ◽  
Toll Like Receptors ◽  
Tlr Signaling ◽  
Animal Data ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Toll-like receptors (TLRs) are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs) recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs) that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1) TLRs, TLR ligands, and the signal transduction system and (2) the important role of TLR signaling in these critical cardiac conditions.

scholarly journals Schistosome tegumental ecto-apyrase (SmATPDase1) degrades exogenous pro-inflammatory and pro-thrombotic nucleotides.

2014 ◽  
Author(s):  
Akram A Da'dara ◽  
Rita Bhardwaj ◽  
Yasser MB Ali ◽  
Patrick Skelly
Keyword(s):  
Thrombus Formation ◽  
Functional Characterization ◽  
Host Cells ◽  
Dependent Manner ◽  
Host Immune Responses ◽  
Genes Encoding ◽  
Molecular Patterns ◽  
Parasitic Worms ◽  
Damage Associated Molecular Patterns

Schistosomes are parasitic worms that can survive in the hostile environment of the human bloodstream where they appear refractory to both immune elimination and thrombus formation. We hypothesize that parasite migration in the bloodstream can stress the vascular endothelium causing this tissue to release chemicals alerting responsive host cells to the stress. Such chemicals are called damage associated molecular patterns (DAMPs) and among the most potent is the proinflammatory mediator, adenosine triphosphate (ATP). Furthermore, the ATP derivative ADP is a pro-thrombotic molecule that acts as a strong activator of platelets. Schistosomes are reported to possess at their host interactive tegumental surface a series of enzymes that could, like their homologs in mammals, degrade extracellular ATP and ADP. These are alkaline phosphatase (SmAP), phosphodiesterase (SmNPP-5) and ATP diphosphohydrolase (SmATPDase1). In this work we employ RNAi to knock down expression of the genes encoding these enzymes in the intravascular life stages of the parasite. We then compare the abilities of these parasites to degrade exogenously added ATP and ADP. . We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade these nucleotides. Suppression of SmAP or SmNPP-5 does not appreciably affect the worms’ ability to catabolize ATP or ADP. These findings are confirmed by the functional characterization of the enzymatically active, full-length recombinant SmATPDase1 expressed in CHO-S cells. The enzyme is a true apyrase; SmATPDase1 degrades ATP and ADP in a cation dependent manner. Optimal activity is seen at alkaline pH. The Km of SmATPDase1 for ATP is 0.4 ±0.02 mM and for ADP, 0.252 ± 0.02 mM. The results confirm the role of tegumental SmATPDase1 in the degradation of the exogenous pro-inflammatory and pro-thrombotic nucleotides ATP and ADP by live intravascular stages of the parasite. By degrading host inflammatory signals like ATP, and pro-thrombotic signals like ADP, these parasite enzymes may minimize host immune responses, inhibit blood coagulation and promote schistosome survival.)

Abstract 288: High Mobility Group Box 1 (HMGB1) is Involved in the Physiopathology of Post-Cardiac Arrest Syndrome

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Emilie Boissady ◽  
Cynthia El Hedjaj ◽  
Matthias Kohlhauer ◽  
Bijan Ghaleh ◽  
Renaud Tissier
Keyword(s):  
Cardiac Arrest ◽  
High Mobility ◽  
Brain Regions ◽  
Clinical Parameter ◽  
High Mobility Group ◽  
Neurological Dysfunction ◽  
Blood Levels ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Introduction: After cardiac arrest, a sepsis-like syndrome is observed and contributes to poor prognosis. Hypothesis: This syndrome could be provoked by the massive release of Damage Associated Molecular Patterns (DAMP). Our aim was to investigate the role of the High mobility group box 1 (HMGB1), a well-characterized nuclear DAMP, in an experimental model of cardiac arrest. Methods: Rabbits were anesthetized and submitted to 10 min of ventricular fibrillation. After resuscitation, they either received an administration of the inhibitor of HMGB1 release glycyrrhizin (4 mg/kg i.v.. (GL group, n=6), or saline (5 ml, i.v.; CT group, n=6). Two additional groups received glycyrrhizin (n=4) or saline (n=4) alone without cardiac arrest (Sham groups). Blood samples were withdrawn to evaluate the kinetics of HMGB1 release. After awakening, survival and neurological dysfunction were evaluated during 3 days. Animals were then euthanized and brain histologic damages were assessed (fluorojade-C staining). Results: In the Sham groups, glycyrrhizin did not modify hemodynamic nor clinical parameter as compared to saline. In the CT group, HMGB1 blood levels increased since 30 min after cardiac arrest and remained elevated until the end of the follow-up. This increase in HMGB1 concentrations was significantly attenuated in GL vs CR (18±1 vs 29±5 and ng/ml at 30 min after cardiac arrest, respectively). Neurological dysfunction score or survival were not significantly improved in GL vs CT (e.g., survival = 50 vs 33 % at day 3 in GT vs CT group). However, fluorojade C staining showed a dramatic attenuation of degenerating neurons in GL vs CT groups in all brain regions (e.g., 7±3 vs 32±10 neurons/field in cortex, respectively). Conclusion: HMGB1 played a key role in early inflammation and promoted neuronal death after cardiac arrest. Its inhibition alone does not provide sufficient benefits to improve the clinical outcome. It emphasizes the importance of other contributors, beyond inflammation and neurons cell death. Adjunction of HMGB1 inhibitors to other therapies could still be of interest.

scholarly journals Role of Damage-Associated Molecular Patterns and Uncontrolled Inflammation in Pediatric Sepsis-Induced Multiple Organ Dysfunction Syndrome

2018 ◽  
Vol 08 (01) ◽  
pp. 025-031 ◽  
Author(s):  
Diana Pang ◽  
Dalia Bashir ◽  
Joseph Carcillo ◽  
Trung Nguyen ◽  
Rajesh Aneja ◽  
...  
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Risk Of Death ◽  
Pediatric Sepsis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Stimulation Of

AbstractThe incidence of multiple organ dysfunction syndrome (MODS) in sepsis varies from 17 to 73% and furthermore, increases the risk of death by 60% when controlled for the number of dysfunctional organs. Several MODS phenotypes exist, each unique in presentation and pathophysiology. Common to the phenotypes is the stimulation of the immune response by pathogen-associated molecular patterns (PAMPs), or danger-associated molecular patterns (DAMPs) causing an unremitting inflammation. Two of the MODS phenotypes are discussed in detail, thrombocytopenia-associated multiple organ failure (TAMOF) and the hyperinflammatory phenotype–macrophage activating syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH). In the end, we will briefly review the role of mitochondrial dysfunction as a significant contributor to the pathogenesis of MODS.

scholarly journals The Role of Peptide Signals Hidden in the Structure of Functional Proteins in Plant Immune Responses

2019 ◽  
Vol 20 (18) ◽  
pp. 4343 ◽  
Author(s):  
Irina Lyapina ◽  
Anna Filippova ◽  
Igor Fesenko
Keyword(s):  
Immune Responses ◽  
Defense Responses ◽  
Innate Immune ◽  
Functional Protein ◽  
Diverse Range ◽  
Peptide Signals ◽  
Plant Pathogen Interactions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Plants have evolved a sophisticated innate immune system to cope with a diverse range of phytopathogens and insect herbivores. Plasma-membrane-localized pattern recognition receptors (PRRs), such as receptor-like kinases (RLK), recognize special signals, pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), and trigger immune responses. A growing body of evidence shows that many peptides hidden in both plant and pathogen functional protein sequences belong to the group of such immune signals. However, the origin, evolution, and release mechanisms of peptide sequences from functional and nonfunctional protein precursors, known as cryptic peptides, are largely unknown. Various special proteases, such as metacaspase or subtilisin-like proteases, are involved in the release of such peptides upon activation during defense responses. In this review, we discuss the roles of cryptic peptide sequences hidden in the structure of functional proteins in plant defense and plant-pathogen interactions.

scholarly journals Laparoscopy in Emergency: Why Not? Advantages of Laparoscopy in Major Emergency: A Review

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 917
Author(s):  
Giuseppe Ietto ◽  
Francesco Amico ◽  
Giuseppe Pettinato ◽  
Valentina Iori ◽  
Giulio Carcano
Keyword(s):  
Laparoscopic Approach ◽  
High Standard ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Surgical Emergencies ◽  
Grade Of Recommendation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Organ Dysfunctions

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, faster recovery and shorter hospital stay. For the remaining surgical emergencies, as well as for abdominal trauma, the role of laparoscopy is still a matter of debate. Patients might benefit from a laparoscopic approach only if performed by experienced teams and surgeons which guarantee a high standard of care. More precisely, laparoscopy can limit damage to the tissue and could be effective for the reduction of the overall amount of cell debris, which is a result of the intensity with which the immune system reacts to the injury and the following symptomatology. In fact, these fragments act as damage-associated molecular patterns (DAMPs). DAMPs, as well as pathogen associated molecular patterns (PAMPs), are recognised by both surface and intracellular receptors of the immune cells and activate the cascade which, in critically ill surgical patients, is responsible for a deranged response. This may result in the development of progressive and multiple organ dysfunctions, manifesting with acute respiratory distress syndrome (ARDS), coagulopathy, liver dysfunction and renal failure. In conclusion, none of the emergency surgical scenarios preclude laparoscopy, provided that the surgical tactic could ensure sufficient cleaning of the abdomen in addition to resolving the initial tissue damage caused by the “trauma”.

Alarmins at the maternal–fetal interface: involvement of inflammation in placental dysfunction and pregnancy complications

2019 ◽  
Vol 97 (3) ◽  
pp. 206-212 ◽  
Author(s):  
Marie-Eve Brien ◽  
Bernadette Baker ◽  
Cyntia Duval ◽  
Virginie Gaudreault ◽  
Rebecca L. Jones ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Deoxyribonucleic Acid ◽  
High Mobility ◽  
Placental Dysfunction ◽  
Current State ◽  
Hofbauer Cells ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
In Pregnancy

Inflammation is known to be associated with placental dysfunction and pregnancy complications. Infections are well known to be a cause of inflammation but they are frequently undetectable in pregnancy complications. More recently, the focus has been extended to inflammation of noninfectious origin, namely caused by endogenous mediators known as “damage-associated molecular patterns (DAMPs)” or alarmins. In this manuscript, we review the mechanism by which inflammation, sterile or infectious, can alter the placenta and its function. We discuss some classical DAMPs, such as uric acid, high mobility group box 1 (HMGB1), cell-free fetal deoxyribonucleic acid (DNA) (cffDNA), S100 proteins, heat shock protein 70 (HSP70), and adenosine triphosphate (ATP) and their impact on the placenta. We focus on the main placental cells (i.e., trophoblast and Hofbauer cells) and describe the placental response to, and release of, DAMPs. We also covered the current state of knowledge about the role of DAMPs in pregnancy complications including preeclampsia, fetal growth restriction, preterm birth, and stillbirth and possible therapeutic strategies to preserve placental function.

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