The role of the complement cascade in endotoxin-induced septic encephalopathy

Jacob, Alexander; Hensley, Lauren K; Safratowich, Bryan D.; Quigg, Richard J.; Alexander, Jessy J.

doi:10.1038/labinvest.3700686

Cited by 61 publications

(62 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, both Lpp and LPS activate the complement cascade, coagulation cascade, and other inflammatory mediators (24)(25)(26)(27). In addition, Lpp purified from Y. enterocolitica synergizes with its LPS to induce production of proinflammatory cytokines in vitro and in vivo, leading to septic shock (28).…”

mentioning

confidence: 99%

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

et al. 2013

View full text Add to dashboard Cite

e Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a ⌬lpp ⌬msbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ⌬msbB single mutant was minimally attenuated, the ⌬lpp single mutant and the ⌬lpp ⌬msbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the ⌬lpp ⌬msbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the ⌬lpp ⌬msbB double mutant, but not the ⌬lpp or ⌬msbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the ⌬lpp ⌬msbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the ⌬lpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the ⌬lpp ⌬msbB double mutant could provide a new live-attenuated background vaccine candidate strain, and this should be explored in the future.

show abstract

mentioning

confidence: 99%

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Salınan bu ajanlar difüzyon yoluyla beynin daha derin dokularına geçebilir, hücre işlev bozukluğuna ve nöronal hücre kaybına neden olur. (7) Bunun sonucunda klinik tabloda işlev bozuklukları, davranış deği-şiklikleri, hatta nörodejenerasyon ile kalı-cı kayıplar görülebilir.…”

Section: Sepsiste Beyin Hasarıunclassified

Neuroprotection in Sepsis by Complement Inhibition and Immunoglobulin Therapy

Şentürk¹,

Esen²

2012

JTAICS

View full text Add to dashboard Cite

ÖZETSon yıllarda birçok nörolojik hastalığın patogenezinde inflamasyonun önemli rol aldığı düşünülmektedir. Nöroinf-lamasyon; inme, travma ve infeksiyon gibi akut nörolojik olaylarda, ayrıca Alzheimer, Parkinson ve multiple skleroz gibi kronik nörodejeneratif hastalıklarda en sık görülen bulgu olarak karşımıza çıkmaktadır. "Nöroinflamasyon hipotezi" beyin hücrelerinin stres ve akut olaylar karşısında nöroinflamasyonu tetikleyerek, inflamasyon yanıtı ile nörodejeneras-yonunu açıklar ve bize nöronal hasar mekanizması için etkili bir nöroprotektif strateji gösterir.Başlangıçta replasman tedavisi olarak düşünülen immünoglobulinler şimdi birçok otoimmün ve sistemik inflamatuvar hastalıkta kullanılmaktadır. İmmünoglobülinler, kompleman aktivasyonun regülasyonun yanı sıra inflamasyon yanıtında, sitokin üretimi ve hücre adezyonunda da düzenleyici roller almaktadırlar. Bu derlemede immünoglobü-lin tedavisinin nöroproteksiyonda etki mekanizmalarını anlatırken, bu konuda yaptığımız son çalışmaya değineceğiz. Bulgularımız sepsiste IVIG kullanımı için rasyonel kanıt oluşturmuştur. Yaptığımız bu son çalışmada, IVIG'in septik sıçanlarda kan beyin-bariyerindeki hasarı azalttığını ve mortaliteyi düşürdüğünü gösterdik. İnme, travma ve sepsis gibi nöröinflamatuar olgularda da IVIG kullanımının nöroprotektif etkisinin olduğunu, potansiyel bir tedavi yöntemi olarak kullanılabileceğini düşünmekteyiz. Anahtar kelimeler: Nöroproteksiyon, sepsis, immunoglobülin SUMMARY Neuroprotection in Sepsis by Complement Inhibition and Immunoglobulin TherapyThe importance of inflammation's role in many neurologic disease pathogenesis has increased rapidly in recent years. Neuroinflammation has been viewed as the most common phenomenon observed in the disorders of the central nervous system, either in the acute insult like infection, trauma, and stroke or in chronic neurodegenerative states like Alsheimer's disease, Parkinson' disease and multiple sclerosis. This "neuroinflammation hypothesis" further challenged the attempts to expand our understanding of neuronal injury and neurodegeneration due to the activation of the brain cells to stress and insult, and targeting neuroinflammation and the major elements of the inflammatory response has become the most effective neuroprotective strategies.Initially introduced as a replacement therapy intravenous immunoglobulin (IVIG) is now widely used for the treatment of a number of autoimmune and systemic inflammatory diseases. Besides these medical conditions, evidence suggests that many other conditions, such as inflammatory disorders with an imbalance in the cytokine network could benefit from immunoglobulin treatment. In this review we would explain the neuroprotective effects of intravenous immunoglobulin mechanisms and the last study we have performed. We recently demonstrated that administration of IVIG to septic rats reduced the amount of BBB (blood-brain barrier) damage and eliminated mortality. We think that the neuroprotective action of IVIG in animal models of different neuroinflammatory injury lik...

show abstract

“…For example, there are widely discussed cytokines such as interleukins (interleukin-1, -6, -10) [37,64], tumor necrosis factor (TNF)-alpha [65,66], complement C5a [67], and cascade [68].…”

Section: Effect Of Cytokine Storm On Brain Functionmentioning

confidence: 99%

In Vivo Imaging of Septic Encephalopathy

Imamura¹,

Murakami²,

Matsumoto³

et al. 2017

Sepsis

View full text Add to dashboard Cite

Septic encephalopathy is a devastating symptom of severe sepsis. Many studies have been performed to uncover the pathophysiological mechanisms of septic encephalopathy; however, novel technical approaches are still required to overcome this complex symptom. Because patients are suffering from severe cognitive impairment, coma, or delirium, which burden not only patients but also caregivers, overcoming septic encephalopathy is still a major social problem worldwide, especially in the intensive care. Septic encephalopathy seems to be caused by cytokine invasion and/or oxidative stress into the brain, and this pathological state leads to imbalance of neurotransmitters. In addition to this pathophysiology, septic encephalopathy causes complicated symptoms (e.g., ischemic stroke, edema, and aberrant sensory function). For these pathophysiological mechanisms, electrophysiology using animal models, positron emission tomography (PET), computed tomography, and magnetic resonance imaging for septic patients has provided important clues. However, the research for septic encephalopathy is currently confronted with the difficulty of complex symptoms. To overcome this situation, in this chapter, we introduce our novel methods for in vivo imaging of septic encephalopathy using near infrared (NIR) nanoparticles, quantum dots. In addition to our recent progress, we propose a strategy for the future approach to in vivo imaging of septic encephalopathy.

show abstract

The role of the complement cascade in endotoxin-induced septic encephalopathy

Cited by 61 publications

References 50 publications

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

Neuroprotection in Sepsis by Complement Inhibition and Immunoglobulin Therapy

In Vivo Imaging of Septic Encephalopathy

Contact Info

Product

Resources

About