Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation

Zhang, Qing; Ain, Qurrat Ul; Schulz, Christian; Pircher, Joachim

doi:10.3389/fimmu.2023.1151926

Cited by 9 publications

(3 citation statements)

References 179 publications

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“…Specifically, cathelicidins in general exhibit low bioavailability and are susceptible to degradation by proteases, thereby restricting feasible routes of administration. Moreover, its pleiotropic nature complicates systemic interventions, requiring precise therapeutic ranges to avoid undesired immunomodulatory effects (Zhang et al, 2023).…”

Section: Limitations In the Therapeutic Use Of Cathelicidinsmentioning

confidence: 99%

Recent Advances in the Therapeutic Potential of Cathelicidins

CONVERSO,

GUERRA,

et al. 2024

Preprint

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Antimicrobial peptides (AMPs) are part of the innate immunity, aiding in the defense against pathogens. Cathelicidins represent a class of cationic AMPs distributed across various organisms, including mammals, birds, reptiles, amphibians, and fish. These peptides perform several important functions for the host, contributing to the direct elimination of pathogens by their microbicidal activities, while also promoting immune modulation, wound healing, and anti-tumor effects. Based on their versatility, cathelicidins have been investigated as therapeutic agents against infections, inflammatory and autoimmune diseases, and tumors. The present review summarizes the most recent discoveries regarding the use of cathelicidins in therapy, while addressing challenges such as cytotoxicity, production costs, and bacterial resistance. Additionally, combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. Despite the vast number of pre-clinical studies, very few peptides have progressed to clinical trials. Nevertheless, the recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics.

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Section: Limitations In the Therapeutic Use Of Cathelicidinsmentioning

confidence: 99%

Recent Advances in the Therapeutic Potential of Cathelicidins

CONVERSO,

GUERRA,

et al. 2024

Preprint

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show abstract

“…Specifically, cathelicidins in general exhibit low bioavailability and are susceptible to degradation by proteases, thereby restricting feasible routes of administration. Moreover, their pleiotropic nature complicates systemic interventions, requiring precise therapeutic ranges to avoid undesired immunomodulatory effects ( Zhang et al, 2023 ).…”

Section: Limitations In the Therapeutic Use Of Cathelicidinsmentioning

confidence: 99%

Recent advances in the therapeutic potential of cathelicidins

Guerra,

Vieira,

Calazans

et al. 2024

Front. Microbiol.

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The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.

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“…It helps maintain Rab in its inactive GDP-bound state, contributing to the precise regulation of intracellular vesicular trafficking and membrane transport. This regulation is essential for normal cell function and for maintaining the structure and function of cell compartments [133,134].…”

Section: Protein Mechanism Referencementioning

confidence: 99%

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action

Serrath,

Pontes,

Paloschi

et al. 2023

Toxins

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L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 μg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO’s ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.

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Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation

Cited by 9 publications

References 179 publications

Recent Advances in the Therapeutic Potential of Cathelicidins

Recent Advances in the Therapeutic Potential of Cathelicidins

Recent advances in the therapeutic potential of cathelicidins

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action

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