Alternative complement pathway activation increases mortality in a model of burn injury in mice.

Gelfand, Jeffrey A.; Donelan, Matthias B.; Hawiger, Alexandra; Burke, John F.

doi:10.1172/jci110715

Cited by 65 publications

(10 citation statements)

References 38 publications

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“…Of course, our mice are untreated, save initial anesthesia and fluid resuscitation, while patients with severe burn are intensively treated. Our observed mortality is similar to that reported by some groups using 25% BSA scald models [ 36 ]. Greater mortality than others might be due to a combination of greater contact in this study due to depilation and use of brass plates, differences in calculating BSA, and conventional versus barrier housing; however, as in patients, lethality and the presence of long-term wasting were well correlated.…”

Section: Discussionsupporting

confidence: 91%

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

Pedroso

Spalding

Cheung

et al. 2012

J cachexia sarcopenia muscle

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BackgroundBurn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking.MethodsYoung adult (12–16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay.ResultsSurvival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects.ConclusionsThis study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.

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Section: Discussionsupporting

confidence: 91%

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

Pedroso

Spalding

Cheung

et al. 2012

J cachexia sarcopenia muscle

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“…Anti-AGM1 Ab depletes NK cells, and anti-NK1.1 Ab depletes both NK and NKT cells for ϳ7 days as we previously reported (24,25). However, the treatment for burned mice with AGM1 Ab or anti-NK1.1 Ab could not effectively deplete the NK/NKT cells, presumably because burn injury has been reported to induce a depletion/inactivation of complements (11)(12)(13)(14), and therefore NK/NKT cells could not be depleted by the combination of Ab and complements. We then injected the mice with these Abs before and after burn injury.…”

Section: In Vivo Depletion Of Nk or Nk/nkt Cellssupporting

confidence: 51%

Restoration of Natural IgM Production from Liver B Cells by Exogenous IL-18 Improves the Survival of Burn-Injured Mice Infected with Pseudomonas aeruginosa

Kinoshita

Shinomiya²,

Ono

et al. 2006

The Journal of Immunology

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Pseudomonas aeruginosa is the most common bacterium of postburn infection. In the present study we investigated the immune mechanism of susceptibility to this type of postburn infection and also examined the efficacy of IL-18 treatment. C57BL/6 mice were challenged with P. aeruginosa on day 7 after burn injury. Although the burn-injured mice showed a poor survival rate after bacterial challenge, they retained their IFN-γ production. The burned mice showed lower serum IgM levels and a poor IgM response following P. aeruginosa challenge in comparison with the sham mice, whereas IL-18 treatment after burn injury (alternate day injections for 1 wk) greatly improved the serum IgM levels, which are P. aeruginosa-independent natural IgM before bacterial challenge, thereby increasing the survival rate after the challenge. IL-18 treatment also induced specific IgM to P. aeruginosa in the sera 5 days after bacterial challenge in the burned mice. Interestingly, CD43+CD5−CD23−B220dim cells, namely B-1b cells, increased in the liver after the IL-18 treatment and were found to actively produce IgM in vitro without any additional stimulation. Furthermore, the IL-18 treatment up-regulated the neutrophil count and the C3a levels in the blood as a result of the increased IgM level, which may thus play a critical role in the opsonization and elimination of any invading bacteria. IL-18 treatment for the burned mice and their resultant natural IgM production were thus found to strengthen the host defense against P. aeruginosa infection.

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“…Gelfand et al . showed that genetic C5 deficiency reduced mortality in the first hours after wounding in a murine model.…”

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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Alternative complement pathway activation increases mortality in a model of burn injury in mice.

Cited by 65 publications

References 38 publications

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

Restoration of Natural IgM Production from Liver B Cells by Exogenous IL-18 Improves the Survival of Burn-Injured Mice Infected with Pseudomonas aeruginosa

Hemocompatibility of different burn wound dressings

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