Lipopolysaccharide, Mediator of Sepsis Enigma: Recognition and Signaling

Bashir, Asma

doi:10.9734/ijbcrr/2011/154

Cited by 9 publications

(3 citation statements)

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“…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).…”

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

et al. 2013

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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.

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

et al. 2013

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“…Lipopolysaccharide is a component of the bacterial outer membrane and a potent stimulator of acute sepsis and chronic inflammation, also known as an endotoxin. [24] Lipopolysaccharide-induced ALI is characterized by severe pulmonary edema and inflammatory cell infiltration in lung tissue. [25] In our study, we found that LPS administration caused a significant increase in the W/D ratio, indicating the occurrence of pulmonary edema and inflammatory cell infiltration consistent with previous studies.…”

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confidence: 99%

Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury in a rat model

Kaya

Polat

et al. 2020

Turk Gogus Kalp Dama

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ÖZAmaç: Bu deneysel çalışmada, doğal bir flavonoid olan hesperetinin sıçanlarda lipopolisakkarit uyarımlı akut akciğer hasar modeli üzerindeki etkileri incelendi. Ça lış m a pl a nı:Mart 2019 -Mayıs 2019 tarihleri arasında ağırlıkları yaklaşık 250-300 g olan toplam 18 erişkin erkek Wistar albino sıçan, kontrol, lipopolisakkarit ve lipopolisakkarit + hesperetin grubu olmak üzere rastgele üç gruba ayrıldı (her grupta n= 6). Akciğer dokusunda ıslak/kuru ağırlık oranı belirlendi. Histopatolojik değişiklikler ışık ve elektron mikroskobu ile incelendi. Pulmoner nükleer faktör-kappa beta, indüklenebilir nitrik oksit sentaz ve alfa-düz kas antijeni indirekt immünohistokimyasal yöntem ile belirlendi. Pulmoner apoptoz, terminal deoksinükleotidil transferaz dUTP çentik uç işaretleme yöntemi ile belirlendi. Tümör nekroz faktör-alfa, interlökin-1 beta, interlökin-6 ve interlökin-10 konsantrasyonları enzim bağlı immunosorbent testi ile belirlendi. Bul gu lar:Hesperetin tedavisi akciğer doku mimarisini anlamlı düzeyde iyileştirdi ve ıslak/kuru ağırlık oranı, nükleer faktör-kappa beta, indüklenebilir nitrik oksit sentaz ve alfa-düz kas antijeni ekspresyonu, pulmoner apoptoz ve proinflamatuvar sitokin düzeylerini azalttı.So nuç: Çalışma sonuçlarımız, hesperetinin sıçanlarda proinflamatuvar sitokin kaskadı, nükleer faktör-kappa beta sinyal yolağı aktivasyonu ve apoptozun baskılanması ile lipopolisakkarit uyarımlı akut akciğer hasarına karşı güçlü bir koruyucu etkiye sahip olduğunu göstermektedir.Anah tar söz cük ler: Akut akciğer hasarı, indüklenebilir nitrik oksit sentaz, lipopolisakkarit, nükleer faktör-kappa beta, pulmoner apoptoz, tümör nekroz faktör-alfa. ABSTRACTBackground: In this experimental study, we aimed to investigate the effects of hesperetin, a natural flavonoid, on a lipopolysaccharideinduced acute lung injury model in rats. Methods:Between March 2019 and May 2019, a total of 18 adult male Wistar albino rats, weighing approximately 250 to 300 g, were randomly divided into three groups as control, lipopolysaccharide, and lipopolysaccharide + hesperetin groups (n=6 in each group). The wet/dry weight ratio of lung tissue was determined. Histopathological changes were examined using light and scanning electron microscopy. Pulmonary nuclear factor-kappa beta, inducible nitric oxide synthase, and alpha-smooth muscle antigen activity were determined with indirect immunohistochemical methods. Pulmonary apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling method. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-10 concentrations were measured with enzyme-linked immunosorbent assay.Results: Treatment with hesperetin significantly improved the architecture of lung tissue and reduced the wet/dry weight ratio, nuclear factor-kappa beta, inducible nitric oxide synthase, and alphasmooth muscle antigen expression, pulmonary apoptosis, and levels of proinflammatory cytokines. Conclusion:Our study results suggest that hesperetin has a potent protective effect aga...

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“…Both Lpp and LPS trigger toxic and biological responses in the hosts through the interaction of their lipid domains with Toll-like receptor 2 (TLR-2) and TLR-4, respectively, and by evoking the production of inflammatory cytokines such as tumor necrosis factor (TNF-␣), interleukin 6 (IL-6), and inter-feron gamma (IFN-␥) (14,15). Also, the complement and coagulation cascades are activated by both Lpp and LPS, and the production of other damaging inflammatory mediators contributes to the severity of infection (14,(16)(17)(18).…”

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Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

et al. 2015

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f Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and ⌬lpp ⌬msbB double mutants. While the ⌬ail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the ⌬lpp ⌬ail double mutant and the ⌬lpp ⌬msbB ⌬ail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD 50 ) equivalent to 6,800 LD 50 s of WT CO92. The mutant-infected animals developed balanced T H 1-and T H 2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD 50 s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the ⌬lpp ⌬msbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a mouse model while retaining the required immunogenicity needed for subsequent protection against infection. P athogenic yersiniae lead to two types of diseases: yersiniosis (typified by gastroenteritis caused by Yersinia enterocolitica and Y. pseudotuberculosis) (1) and plague (evoked by Y. pestis) (2, 3). Y. pestis has evolved from Y. pseudotuberculosis within the last 20,000 years by acquiring additional plasmids and pathogenicity islands as well as by deactivating some genes (4-6). This evolutionary adaptation allowed the plague bacterium to maintain a dual life-style in fleas and rodents/mammals and conferred the ability to survive in the blood instead of the intestine (3). Plague manifests itself in three forms: bubonic (acquired from an infected rodent through a flea bite), pneumonic (acquired either directly by aerosol transmission from an infected host's lungs through respiratory droplets or secondarily from bubonic plague), and septicemic (severe bacteremia either directly due to a flea bite or subsequent to bubonic or pneumonic plague) (2). T...

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Lipopolysaccharide, Mediator of Sepsis Enigma: Recognition and Signaling

Cited by 9 publications

References 67 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

Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury in a rat model

Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

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