Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

Chakraborty, Shinjini; Winkelmann, Veronika Eva; Braumüller, Sonja; Palmer, Annette; Schultze, Anke; Klohs, Bettina; Ignatius, Anita; Vater, Axel; Fauler, Michael; Frick, Manfred; Huber‐Lang, Markus

doi:10.1038/s41598-020-79607-1

Cited by 10 publications

(4 citation statements)

References 56 publications

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“…Polarization of neutrophils to the N2 type exhibits a longer lifespan and releases IL-6 and NET to promote cancer development (Wang et al 2018 ). Moreover, C5aR1-knock-down animals has a lower MPO level in lung of mice with polytrauma and hemorrhagic shock (Chakraborty et al 2021 ). Additionally, the PAD4 is a crux of the NET formation (Hawez et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap

Shen,

Zeng

et al. 2024

J Mol Histol

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Sepsis has a systemic inflammatory response syndrome caused by infection. While neutrophils play contradictory roles in different stages of sepsis. Neutrophils have been proven to play an antibacterial role by producing neutrophil extracellular traps (NETs). Although the NET is beneficial to bacteria resistance, abnormal NET increases tissue damage. The complement C5a receptor 1 (C5ar1) is a gene related to strong inflammatory reactions and is found to be associated with inflammatory factors. This study found that there were 45 down-regulated genes and 704 up-regulated genes in sepsis rats by transcriptome sequencing. And those genes were significantly related to inflammation and immunity by GO and KEGG enrichment analysis involving the chemokine signaling pathway, the Toll-like receptor (TLR) signaling pathway, and the Fc gamma R-mediated phagocytosis. Additionally, the C5ar1 gene was significantly upregulated with interesting potential in sepsis and used for further study. This study used cecum ligation and puncture (CLP) rats that were respectively injected intravenously with PBS or the lentivirus vector to explore the effect of C5ar1 on CLP rats. It demonstrated that silenced- C5ar1 inhibited the ALT, AST, BUN, and CREA levels, improved the lung and spleen injury, and reduced the TNF-α, IL-6, IL-1β, IL-10, cf-DNA, and cfDNA/MPO levels. Additionally, silenced C5ar1 inhibited the TLR2, TLR4, and peptidylarginine deiminase 4 expression levels, which suggested the improvement of silenced C5ar1 on sepsis via inhibiting NETs and the TLR signaling pathway. This study provides a basis and new direction for the study of treatment on sepsis.

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Section: Discussionmentioning

confidence: 99%

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap

Shen,

Zeng

et al. 2024

J Mol Histol

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“…Copyright 2017 Qiaozhi Lu et al (changes were made). (1D) Alveolar-capillary barrier models on permeable 0.4 μm pore size polyester membranes which can be introduced to an air–liquid interface represents the ease of handling coculture barriers on such mechanically robust platforms; adapted with permission from ref ( 165 ). Copyright 2021 Shinjini Chakraborty et al (changes were made).…”

Section: Porous Polymeric Membranes As Bm Mimicsmentioning

confidence: 99%

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering

et al. 2022

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Advancements in the field of tissue engineering have led to the elucidation of physical and chemical characteristics of physiological basement membranes (BM) as specialized forms of the extracellular matrix. Efforts to recapitulate the intricate structure and biological composition of the BM have encountered various advancements due to its impact on cell fate, function, and regulation. More attention has been paid to synthesizing biocompatible and biofunctional fibrillar scaffolds that closely mimic the natural BM. Specific modifications in biomimetic BM have paved the way for the development of in vitro models like alveolar-capillary barrier, airway models, skin, blood-brain barrier, kidney barrier, and metastatic models, which can be used for personalized drug screening, understanding physiological and pathological pathways, and tissue implants. In this Review, we focus on the structure, composition, and functions of in vivo BM and the ongoing efforts to mimic it synthetically. Light has been shed on the advantages and limitations of various forms of biomimetic BM scaffolds including porous polymeric membranes, hydrogels, and electrospun membranes This Review further elaborates and justifies the significance of BM mimics in tissue engineering, in particular in the development of in vitro organ model systems.

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“…Independently of the initial infectious trigger, the cell-destructive activities of complement and other pathways may eventually lead to tissue damage, multi-organ failure, and death. While several pathways and effectors may be involved in the process, the release of the anaphylatoxin C5a and its signaling via C5a receptor 1 (C5aR1) have been most closely linked to an adverse outcome [ 58 ]. In trauma, the exposure to microbes but also the inflicted tissue damage and/or hypoxia after injury may cause SIRS and negatively affect the clinical prognosis.…”

Section: The Thin Line Between Defense and Distress: Complement’s Pathological Sidementioning

confidence: 99%

Tipping the balance: intricate roles of the complement system in disease and therapy

Pouw

Ricklin

2021

Semin Immunopathol

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The ability of the complement system to rapidly and broadly react to microbial intruders, apoptotic cells and other threats by inducing forceful elimination responses is indispensable for its role as host defense and surveillance system. However, the danger sensing versatility of complement may come at a steep price for patients suffering from various immune, inflammatory, age-related, or biomaterial-induced conditions. Misguided recognition of cell debris or transplants, excessive activation by microbial or damaged host cells, autoimmune events, and dysregulation of the complement response may all induce effector functions that damage rather than protect host tissue. Although complement has long been associated with disease, the prevalence, impact and complexity of complement’s involvement in pathological processes is only now becoming fully recognized. While complement rarely constitutes the sole driver of disease, it acts as initiator, contributor, and/or exacerbator in numerous disorders. Identifying the factors that tip complement’s balance from protective to damaging effects in a particular disease continues to prove challenging. Fortunately, however, molecular insight into complement functions, improved disease models, and growing clinical experience has led to a greatly improved understanding of complement’s pathological side. The identification of novel complement-mediated indications and the clinical availability of the first therapeutic complement inhibitors has also sparked a renewed interest in developing complement-targeted drugs, which meanwhile led to new approvals and promising candidates in late-stage evaluation. More than a century after its description, complement now has truly reached the clinic and the recent developments hold great promise for diagnosis and therapy alike.

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Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

Cited by 10 publications

References 56 publications

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering

Tipping the balance: intricate roles of the complement system in disease and therapy

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