Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress

Han, Chang Yeop; Pichon, Trey J.; Wang, Xu; Ringgold, Kristyn M.; John, Alexander E. St.; Stern, Susan A.; White, Nathan J.

doi:10.1016/j.redox.2022.102263

Cited by 10 publications

(10 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 The reduction in clot strength evidenced by TEG could also be attributable to the significant changes that occur in fibrinogen coagulability during inflammation as evidenced by Han et al: indeed, fibrinogen is sequentially oxidized and degraded during exposure to leukocyte activation and inflammation. 24 When the effect of AT supplementation onto the relationship between TEG variables and cytokines was evaluated, most of the modifications involved TEG-MA. Indeed, patients receiving AT supplementation showed negative correlation between TEG-MA and IL-6 instead of a positive correlation shown by the controls, or they showed further negative correlation in the case of IL-8 and Pro-ADM. From a clinical point of view, AT supplementation in this context seems to contribute to clot weakness as the concentration of the abovementioned cytokines rises.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure

Meli,

De Falco,

Novembrino

et al. 2024

Perfusion

View full text Add to dashboard Cite

Introduction Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG. Methods This is a pre-specified sub-study of the “Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation” study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1β, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points. Results Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines. Conclusions High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure

Meli,

De Falco,

Novembrino

et al. 2024

Perfusion

View full text Add to dashboard Cite

show abstract

“…Neutrophils have been reported to phagocytose tumor debris and directly kill tumor cells by producing high levels of myeloperoxidase, ROS, hypochlorite acid, and other cytotoxic agents. [44,45] In addition, neutrophils are important effector cells in antibody-mediated immunotherapies. Binding between the Fc segment of the antibody and the Fc receptor on the surface of neutrophils induces the release of a cytotoxic medium that kills tumor cells.…”

Section: Fe 3 O 4 @Ir820@cpg Activates Anti-tumor Immune Systemsmentioning

confidence: 99%

Laser‐Activatable In Situ Vaccine Enhances Cancer‐Immunity Cycle

Wang,

You,

et al. 2023

Advanced Materials

View full text Add to dashboard Cite

The immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address a single key aspect to enhance anti‐tumor immunity. In the present study, we developed a nanoplatform (Fe3O4@IR820@CpG)‐based immunotherapy strategy that targets the multiple key steps in cancer‐immunity cycle: 1) promotes the release of tumor‐derived proteins (TDPs), including tumor‐associated antigens and pro‐immunostimulatory factors), in addition to the direct killing effect, by photothermal (PTT) and photodynamic therapy (PDT); 2) captures the released TDPs and delivers them, together with CpG (a Toll‐like receptor 9 [TLR‐9] agonist) to antigen presenting cells (APCs) to promote antigen presentation and T cell activation; 3) enhances the tumor‐killing ability of T cells by combining with anti‐programmed death ligand 1 antibody (α‐PD‐L1), which collectively advances our outstanding of the anti‐tumor effects on colorectal, liver and breast cancers. The broad‐spectrum anti‐tumor activity of Fe3O4@IR820@CpG with α‐PD‐L1 demonstrated that optimally manipulating anti‐cancer immunity not singly but as a group provides promising clinical strategies.This article is protected by copyright. All rights reserved

show abstract

“…However, fibrinogen is also directly modified by inflammation-induced oxidative stress and proteolysis that can impair its function. 50,51 Increased oxidation of the important fibrinogen A-αC domain has also been documented in preclinical models and trauma patients with bleeding coagulopathy, suggesting a potential direct link between inflammation, oxidative stress, and coagulopathy. 52,53…”

Section: Applying Lessons Learned For Managing Hemostasis On Earth An...mentioning

confidence: 99%

Managing Hemostasis in Space

White,

Wenthe

2023

ATVB

Self Cite

View full text Add to dashboard Cite

Human space travel requires exposure to weightlessness, ionizing radiation, isolation, and austerity. A recent report of internal jugular vein thrombosis in astronauts in low Earth orbit confirms that these exposures also affect vascular biology to influence diseases of thrombosis and hemostasis. This brief review summarizes the known influences of space travel on inflammation, blood coagulation, and the cardiovascular system and conceptualizes how they might combine to affect thrombosis and hemostasis. In the event of a major thrombotic or bleeding emergency, it is anticipated that the unique physiological influences of the space environment and logistical limitations of providing medical care in space would require a response that is unique from our current experience. We also look towards the future to discuss lessons learned from our current experiences on Earth and in space.

show abstract

Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress

Cited by 10 publications

References 47 publications

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure

Laser‐Activatable In Situ Vaccine Enhances Cancer‐Immunity Cycle

Managing Hemostasis in Space

Contact Info

Product

Resources

About