The role of complement in the acute phase response after burns

Korkmaz, Halil İbrahim; Krijnen, Paul A.J.; Ulrich, Magda M. W.; Jong, Evelien de; Zuijlen, Paul P. M. van; Niessen, Hans W.M.

doi:10.1016/j.burns.2017.03.007

Cited by 32 publications

(26 citation statements)

References 90 publications

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“…Specifically our study revealed that factor H is contributed by MSCs. Others reported that factor H is necessary to preserve myocardium and myocardial function in chronic MI and promote tissue healing 28 , 36 , 37 . Thus, to delicately modulate, rather than to abruptly blunt, complement activation may be an approach for cardiac repair.…”

Section: Discussionmentioning

confidence: 99%

Analysis of mesenchymal stem cell proteomes in situ in the ischemic heart

et al. 2020

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Rationale: Cell therapy for myocardial infarction is promising but largely unsuccessful in part due to a lack of mechanistic understanding. Techniques enabling identification of stem cell-specific proteomes in situ in the injured heart may shed light on how the administered cells respond to the injured microenvironment and exert reparative effects. Objective: To identify the proteomes of the transplanted mesenchymal stem cells (MSCs) in the infarcted myocardium, we sought to target a mutant methionyl-tRNA synthetase (MetRS L274G ) in MSCs, which charges azidonorleucine (ANL), a methionine analogue and non-canonical amino acid, to tRNA and subsequently to nascent proteins, permitting isolation of ANL-labeled MSC proteomes from ischemic hearts by ANL-alkyne based click reaction. Methods and Results: Murine MSCs were transduced with lentivirus MetRS L274G and supplemented with ANL; the ANL-tagged nascent proteins were visualized by bio-orthogonal non-canonical amino-acid tagging, spanning all molecular weights and by fluorescent non-canonical amino-acid tagging, displaying strong fluorescent signal. Then, the MetRS L274G -transduced MSCs were administered to the infarcted or Sham heart in mice receiving ANL treatment. The MSC proteomes were isolated from the left ventricular protein lysates by click reaction at days 1, 3, and 7 after cell administration, identified by LC/MS. Among all identified proteins (in Sham and MI hearts, three time-points each), 648 were shared by all 6 groups, accounting for 82±5% of total proteins in each group, and enriched under mitochondrion, extracellular exosomes, oxidation-reduction process and poly(A) RNA binding. Notably, 26, 110 and 65 proteins were significantly up-regulated and 11, 28 and 19 proteins were down-regulated in the infarcted vs. Sham heart at the three time-points, respectively; these proteins are pronounced in the GO terms of extracellular matrix organization, response to stress and regulation of apoptotic process and in the KEGG pathways of complements and coagulation cascades, apoptosis, and regulators of actin cytoskeleton. Conclusions: MetRS L274G expression allows successful identification of MSC-specific nascent proteins in the infarcted hearts, which reflect the functional states, adaptive response, and reparative effects of MSCs that may be leveraged to improve cardiac repair.

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Section: Discussionmentioning

confidence: 99%

Analysis of mesenchymal stem cell proteomes in situ in the ischemic heart

et al. 2020

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“…showed that genetic C5 deficiency reduced mortality in the first hours after wounding in a murine model. Complement activation can cause adverse effects in patients, like delayed wound healing and acute phase response as well as local tissue damage, which can lead to negative systemic effects in several organs and might be a predictor for clinical outcome in burn patients . Furthermore, in their animal study, Mulligan et al .…”

Section: Discussionmentioning

confidence: 99%

Hemocompatibility of different burn wound dressings

Denzinger

Held

Scheffler

et al. 2019

Wound Repair Regeneration

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A variety of wound dressing are available for burns. Furthermore, although their impacts on wound healing have been studied sufficiently, their effects on blood remain unclear. Meanwhile, this aspect is extremely important, since blood interacts with the wound dressing, especially in extensive burn injuries. Therefore, the aim of this study is to evaluate the hemocompatibility and immunogenicity of different burn wound dressings. Accordingly, human whole blood (n = 5) was anticoagulated with heparin, treated with different wound dressings and incubated at 37 C for 30 minutes. Different parameters for coagulation and hemocompatibility were evaluated before and after incubation. Consequently, Jelonet, Xenoderm, and Matriderm showed higher TAT-III concentrations, Jelonet, Xenoderm, EZ Derm, and Matriderm were higher β-thromboglobulin; EZ Derm and Burntec showed higher SC5b-9 concentrations after incubation with whole blood. Our ex vivo study provided initial insights into the hemocompatibility and immunogenicity of different burn wound dressings. Moreover, Xenografts (Xenoderm and EZ Derm), Jelonet and Matriderm showed a hemostyptic effect, while EZ Derm and Burntec activated the complement system. Therefore, further studies must be conducted to analyze the possible effects in vivo. Hemocompatibility of different burn wound dressingsDenzinger et al.

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“…Part of the innate immune response, the complement system is made up of a number of complement (C) proteins which enhance the ability to fight infection by both directly and indirectly attacking microbes and clearing debris [46]. The complement system is dynamically involved with the cellular immune response, operating via different pathways including the classical, lectin and alternate pathways or via properdin and thrombin, triggered by antibodies expressed on apoptotic cells or microbes, by distinct carbohydrate and lipid residues on injured cells and by DAMPs and PAMPs in the wound site [37,[47][48][49]. Whilst the different pathways are employed, all complement cascades act to lyse microbes via the formation of C5b and C9 into the membrane attack complex and converge to produce C3a which together with C5 attracts inflammatory cells and promotes phagocytosis and clearance of damaged cells by macrophages [42,47].…”

Section: Complement Activationmentioning

confidence: 99%

The Role of the Inflammatory Response in Burn Injury

Strudwick¹,

Cowin²

2018

Hot Topics in Burn Injuries

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Burns are characterised by significant local swelling and redness around the site of injury, indicative of acute inflammation. Whilst the inflammatory response is fundamental to the healing process, triggering a cascade of cytokines and growth factors to protect against the risk of infection, it is clear that prolonged inflammation can be detrimental and lead to scarring and fibrosis. Severe burns may display chronic, persistent inflammation long after the initial burn injury and may even result in multiple organ failure (MOF) due to systemic inflammatory response syndrome (SIRS). Excessive inflammation in the early stages of healing has been identified as a causative factor in the formation of scars which can be disfiguring, functionally restrictive and may require revisionary surgeries. Therefore, it is imperative that inflammation is effectively managed following burn injuries in order to optimise the benefits it provides whilst actively preventing the complications of inflammation including SIRS, multiple organ failure (MOF) and the development of scarring and fibrosis. Reviewing the current knowledge about the role of the inflammatory response in burns and the treatments available for the management of inflammation during wound healing, highlights the importance of continued research into understanding and developing new approaches to regulate inflammatory responses post-burn injuries.

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The role of complement in the acute phase response after burns

Cited by 32 publications

References 90 publications

Analysis of mesenchymal stem cell proteomes in situ in the ischemic heart

Analysis of mesenchymal stem cell proteomes in situ in the ischemic heart

Hemocompatibility of different burn wound dressings

The Role of the Inflammatory Response in Burn Injury

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