Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice

Ha, Tuanzhu; Fang, Hua; Grant, Daniel; Xia, Yeling; Ma, Jing; Gao, Xiang; Kelley, Jim; Williams, David L.; Kalbfleisch, John H.; Browder, I. William; Kao, Race L.; Li, Chuanfu

doi:10.1152/ajpheart.01264.2005

Cited by 42 publications

(98 citation statements)

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“…77,78 In line with these findings, the antiinflammatory mediator glucan phosphate, known to attenuate cardiac dysfunction and to improve survival rates in septic mice, has recently been shown to act by inhibiting the cardiac expression of MIF and reducing cardiomyocyte apoptosis. 79 Similarly, MIF has been shown to mediate the late and prolonged cardiac depression after burn injury associated with major tissue damage that was restored by anti-MIF treatment. 80 Notably, an increase in MIF within the alveolar space during late experimental sepsis or MIF instilled exogenously into the lungs induced kinase activation and phosphorylation in the heart, eg, of MAPK, as indicative of myocardial depression, suggesting that MIF released from the lungs during sepsis may in part be responsible for the cardiac dysfunction accompanying sepsis.…”

Section: Mif Contributes To Myocardial Dysfunction and Sepsismentioning

confidence: 99%

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

2008

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Abstract-The highly conserved and archetypical yet atypical cytokine macrophage migration inhibitory factor (MIF) fulfills pleiotropic immune functions in many acute and chronic inflammatory diseases. Recent evidence has emerged from both expression and functional studies to implicate MIF in various aspects of cardiovascular disease. The present review is aimed at providing a synopsis of the involvement of MIF in the inflammatory pathogenesis of atherosclerosis and its consequences, namely unstable plaque formation, remodeling after arterial injury, aneurysm formation, myocardial infarction, or ischemia-reperfusion injury. In addition, other forms of myocardial dysfunction and inflammation and the role of MIF in angiogenesis are reviewed. The functional data are reconciled with recent progress in the identification of heptahelical (CXC chemokine) receptors for MIF, its prototypic role as their noncanonical ligand, and its signal transduction profile operative in atherogenic and inflammatory recruitment of mononuclear cells and in the oxidative damage and apoptosis of cardiomyocytes. Its unique features and functions clearly distinguish MIF from other cytokines implicated in atherogenesis and make it a prime target for achieving therapeutic regression of atherosclerosis.

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Section: Mif Contributes To Myocardial Dysfunction and Sepsismentioning

confidence: 99%

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

2008

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“…As an example, lipopolysaccharide (LPS) challenge results in significant cardiac dysfunction mediated by NF-B activation (12). We have previously reported that cardiac function was significantly depressed in CLPinduced septic mice (9). We also reported that administration of glucan phosphate (GP) significantly improved cardiac function in CLP sepsis (9) and increased long-term survival (30).…”

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confidence: 99%

Glucan phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-κB activation

Xia

Liu³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-B activation. Am J Physiol Heart Circ Physiol 301: H848 -H855, 2011. First published June 3, 2011 doi:10.1152/ajpheart.01007.2010.-Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. High-mobility group box 1 (HMGB1) serves as a late mediator of lethality in sepsis. We have reported that glucan phosphate (GP) attenuates cardiac dysfunction and increases survival in cecal ligation and puncture (CLP)-induced septic mice. In the present study, we examined the effect of GP on HMGB1 translocation from the nucleus to the cytoplasm in the myocardium of septic mice. GP was administered to mice 1 h before induction of CLP. Sham-operated mice served as control. The levels of HMGB1, Toll-like receptor 4 (TLR4), and NF-B binding activity were examined. In an in vitro study, H9C2 cardiomyoblasts were treated with lipopolysaccharide (LPS) in the presence or absence of GP. H9C2 cells were also transfected with Ad5-IB␣ mutant, a super repressor of NF-B activity, before LPS stimulation. CLP significantly increased the levels of HMGB1, TLR4, and NF-B binding activity in the myocardium. In contrast, GP administration attenuated CLP-induced HMGB1 translocation from the nucleus to the cytoplasm and reduced CLP-induced increases in TLR4 and NF-B activity in the myocardium. In vitro studies showed that GP prevented LPS-induced HMGB1 translocation and NF-B binding activity. Blocking NF-B binding activity by Ad5-IB␣ attenuated LPSinduced HMGB1 translocation. GP administration also reduced the LPS-stimulated interaction of HMGB1 with TLR4. These data suggest that attenuation of HMGB1 translocation by GP is mediated through inhibition of NF-B activation in CLP-induced sepsis and that activation of NF-B is required for HMGB1 translocation.high-mobility group box 1; myocardium; nuclear factor-B HIGH-MOBILITY GROUP BOX 1 (HMGB1) is an evolutionarily conserved protein present in the nucleus of almost all eukaryotic cells where it functions to stabilize nucleosomes and acts as a transcription factor (4,14,25,28). Recent evidence suggests that HMGB1 is an important danger-associated molecular pattern (DAMP) (14, 28) and is actively secreted by activated macrophages and released from necrotic (25) and damaged tissues (4). In vivo neutralization of HMGB1 by specific antibodies protects mice against lethal endotoxemia and sepsis (28), as well as endotoxin-induced acute lung injury (29). More significantly, anti-HMGB1 antibodies rescued mice from lethal sepsis even when the first dose of antibodies was given as late as 24 h after cecal ligation and puncture (CLP) surgery (29). These data suggest that HMGB1 serves as a late mediator of lethality in sepsis (6,28). In vitro studies have demonstrated that the HMGB1-stimulated inflammatory response could be mediated through receptors for advanced glycation end products (RAGE) (27), Toll-like receptor 2 (TLR2), TLR4 (23, 24), and TLR9 (26).TLR-mediated sig...

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“…Przeprowadzone dotychczas badania wskazują, że uszkodzenie serca wiąże się głównie ze zmianami czynnościowymi [15]. Mimo że stwierdzono na modelu zwierzęcym istotne zmiany apoptyczne włókien mięśniowych, praktyka kliniczna pokazuje, że występujące zaburzenia funkcji serca nie są adekwatne do tego typu zmian [13,16,17]. Prawdopodobnie dysfunkcja związana jest głównie z efektem cytokinowym i w znaczącym stopniu jest odwracalna.…”

Section: Histopathological Examinationunclassified

“…Studies conducted to date demonstrate that cardiac damage is mainly related to functional changes [15]. Although significant apoptotic lesions in muscle fibres have been shown in the animal model, clinical practice demonstrates that identified cardiac function disorders are not consistent with lesions of this type [13,16,17]. The dysfunction is probably linked to the cytokine effect and is largely reversible.…”

Section: Histopathological Examinationmentioning

confidence: 99%

Post-mortem diagnostics in cases of sepsis. Part 2. Biochemical and morphological examinations

Rorat¹,

Simon²

2015

amsik

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StreszczenieWspółczesna pośmiertna diagnostyka sepsy pozwala na uzyskanie wielu przydatnych z punktu widzenia medycyny sądowej dowodów weryfikujących przyczynę zgonu. Liczne doniesienia wskazują na przydatność oznaczeń wskaźni-ków stanu zapalnego stosowanych w medycynie klinicznej, głównie białka C-reaktywnego i prokalcytoniny. Podczas sądowo-lekarskiej sekcji zwłok niezbędne staje się wnikliwe poszukiwanie objawów chorobowych i ognisk zapalnych podczas oględzin zewnętrznych i wewnętrznych. Mimo że brak jest patognomonicznych dla sepsy zmian w badaniu histopatologicznym, stanowi ono nieodzowny element diagnostyki pośmiertnej. Interpretacja uzyskanych danych i ustalenie przyczyny zgonu wymaga jednoczesnej oceny okoliczności śmierci, objawów klinicznych, wyników badań mikrobiologicznych, badań biochemicznych, ustaleń sekcyjnych i wyników badań histopatologicznych.Słowa kluczowe: błąd opiniodawczy, zakażenie inwazyjne, mediatory zapalne, badanie mikroskopowe. AbstractContemporary post-mortem diagnostics of sepsis makes it possible to obtain multiple evidence verifying the cause of death which is valuable for forensic medicine. There are a number of reports indicating the usefulness of tests of inflammatory markers (chiefly C-reactive protein and procalcitonin) that are employed in clinical medicine. During medico-legal autopsy, it becomes necessary to perform a careful search of pathological symptoms and inflammatory foci -both during external and internal examinations. Although sepsis lacks pathognomonic lesions that can be identified by histopathological examination, it represents an intrinsic element of post-mortem diagnostics. In order to be able to interpret the findings and establish the cause of death, the evaluation must concurrently take into account the circumstances of death, clinical symptoms, results of microbiological and biochemical tests, autopsy findings and histopathological examination results.

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Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice

Cited by 42 publications

References 50 publications

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

Glucan phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-κB activation

Post-mortem diagnostics in cases of sepsis. Part 2. Biochemical and morphological examinations

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