Innate response to self-antigen significantly exacerbates burn wound depth

Suber, Freeman; Carroll, Michael; Moore, Francis D.

doi:10.1073/pnas.0609026104

Cited by 48 publications

(47 citation statements)

References 29 publications

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“…Experiments in different animal burn models with either soluble complement receptor 1, an inhibitor of complement activation by both classical and alternative pathway, or C1 inhibitor showed that complement inhibition led to reduced neutrophil infiltration and reduced burn wound severity. [11][12][13]27 In addition to reduced tissue damage, local inhibition of inflammation may also reduce systemic complications. A recent study showed that attenuating burn wound inflammation by a locally administered p38 mitogen-activated protein kinase inhibitor improved survival in mice, 28 indicating that, indeed, attenuation of local burn wound inflammation may effect the systemic inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 In line with this, in complement factor C4 knock-out mice, burn wounds healed without contracture or scarring, whereas in burn wound healing in wild-type mice, scarring and contracture occurred. 13 Postburn blood levels of CRP were shown to be not only proportional with the extent of the burn wound area but also with the depth of the wound. 14,15 Interestingly, in nonburn wounds CRP was shown to activate complement locally on a tissue level in various inflammatory diseases, such as myocardial infarction 16 and atherosclerosis.…”

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confidence: 98%

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Acute Inflammation is Persistent Locally in Burn Wounds: A Pivotal Role for Complement and C-Reactive Protein

Goot

Krijnen

Begieneman

et al. 2009

Journal of Burn Care & Research

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Severe burns can cause major complications, such as infection and deforming scar formation. Burn wounds induce an excessive inflammatory response. Serum levels of complement and the acute phase reactant C-reactive protein (CRP) are upregulated in response to burn injury and have been shown to be related to the severity of burn trauma and to the clinical outcome. However, complement and CRP have not been investigated on a tissue level locally at the site of the burn trauma. Protein levels and localization of complement activation product C3d and CRP were determined semi-quantitatively in burn eschar between 2 and 46 days after injury, using immunohistochemistry. CD68 and myeloperoxidase (MPO), markers for macrophages and neutrophilic granulocytes, respectively, were also analyzed on these biopsies. Skin biopsies of very recent surgical wounds (seconds old) served as controls. C3d and CRP are present at high levels in the burn wound. Protein levels of both mediators are significantly elevated up to at least 46 days after injury in comparison with control wounds. In line with this, neutrophils and macrophages infiltrate the burn wound in high numbers up to at least 46 days after injury. The excessive presence of the inflammatory mediators, complement and CRP, and the increased infiltration of neutrophils and macrophages in burn woundsup to 46 days after injury implicate a persistent ongoing acute inflammation locally in the burn wound up to weeks after the initial trauma. (J Burn Care Res 2009;30:274 -280)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Acute Inflammation is Persistent Locally in Burn Wounds: A Pivotal Role for Complement and C-Reactive Protein

Goot

Krijnen

Begieneman

et al. 2009

Journal of Burn Care & Research

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“…Thus, they found that pretreatment with systemic N2 peptide (a peptide that binds IgM) or posttreatment with topical N2 peptide blocks inflammatory exacerbation of burn wound injury. 50 Once leukocytes are attracted to a site of burn injury, whether by complement breakdown products or other mediators, they adhere to the vascular endothelium through interactions between leukocyte surface receptors and specialized ligands on the endothelial surface. In a rabbit burn model, the effect of an antibody to CD18 (MAb 60.3) on wound healing was tested.…”

Section: Neutrophil Aggregation Venule Occlusion and Cytokine Produmentioning

confidence: 99%

A Review of the Local Pathophysiologic Bases of Burn Wound Progression

Shupp

Nasabzadeh

Rosenthal

et al. 2010

Journal of Burn Care & Research

193

151

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Burn wound progression refers to the phenomenon of continued tissue necrosis in the zone of stasis after abatement of the initial thermal insult. A multitude of chemical and mechanical factors contribute to the local pathophysiologic process of burn wound progression. Prolonged inflammation results in an accumulation of cytotoxic cytokines and free radicals, along with neutrophil plugging of dermal venules. Increased vascular permeability and augmentations of interstitial hydrostatic pressure lead to edema with vascular congestion. Hypercoagulability with thrombosis further impairs blood flow, while oxidative stress damages endothelial cells and compromises vascular patency. A number of studies have investigated the utility of various agents in modulating these mechanisms of burn wound progression. However, as many of studies have used animal models of burn injury, often with administration of therapy preburn, obscuring the clinical applicability of the results to burn patients is of questionable benefit. An understanding of the complex, interrelated mediators of burn wound progression and their ultimate point of convergence in effecting tissue necrosis—cell apoptosis or oncosis—will allow for the future development of therapeutic interventions.

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“…However, the inflammatory cascade often goes uncontrolled and results in excessive production of proinflammatory cytokines, leading to local tissue edema, ischemia, and consequently progressive injury of burn wounds. 7,8 The essence of inflammation after burn or trauma is the activation of innate immunity. The immune system recognizes danger signals released from tissue injury or pathogens through pattern recognition receptors.…”

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confidence: 99%