Role of nitric oxide in the circulatory failure and organ injury in a rodent model of Gram‐positive shock

Kengatharan, Ken M.; Kimpe, Sjef J. De; Thiemermann, Christoph

doi:10.1111/j.1476-5381.1996.tb16053.x

Cited by 95 publications

(73 citation statements)

References 55 publications

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“…Rolipram, a putative selective inhibitor of phosphodiesterase type IV (12), reportedly was able to reduce TNF-a production in vitro (13,14) and in vivo (15). Collectively, published data in the literature seems to support the view that in septic shock, cardiovascular collapse results from an increase in plasma TNF-a that eventually results in an over-production of NO which produces vascular hyporeactivity and collapse of the cardiovascular system (9,16). Recently, it has been suggested that phosphodiesterase type IV inhibitors are capable of inhibiting the expression, and thus reducing the production and release, of this cytokine (17).…”

supporting

confidence: 51%

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

Dutta

Ryan

Tabrizchi

2001

Japanese Journal of Pharmacology

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ABSTRACT-Administration of bacterial endotoxin (lipopolysaccharide, LPS) intravenously has been noted to produce a shock state, which is characterized by hypotension and mutli-organ system failure. The aim of the present investigation was to (a) examine the influence of rolipram on hemodynamics, plasma levels of tumor necrosis factor-a (TNF-a) levels, and production of inducible nitric oxide synthase (iNOS) in the lungs, ex vivo, in LPS-treated rats, and (b) determine the cardiovascular effects of a selective a1-adrenoceptor agonist, methoxamine, in the absence or presence of rolipram in rats treated with LPS. Blood pressure, cardiac index, heart rate and arterial resistance were assessed in Long-Evans rats anesthetized with thiobutabarbital. Administration of LPS to animals resulted in a significant reduction in cardiac index over time. The administration of LPS to rats resulted in a substantial rise in the plasma levels of TNF-a. Furthermore, the injection of LPS resulted in a significant increase in the iNOS activity in the lungs. Pre-treatment with rolipram prevented the decline in cardiac index in animals that received LPS. Infusion of methoxamine into animals injected with rolipram and pre-treated with LPS did not result in significant changes in cardiac index. Pre-treatment with rolipram or dexamethasone in animals injected with LPS significantly prevented the rise in TNF-a when compared to the respective values in vehicle-treated animals. Our present observations support the view that the cardiac index can be maintained in animals treated with LPS independent of iNOS inhibition.

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supporting

confidence: 51%

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

Dutta

Ryan

Tabrizchi

2001

Japanese Journal of Pharmacology

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“…Like LPS, LTA will induce shock in laboratory animals (Lonchampt et al 1992, Kengatharan et al 1996a and NOSII in macrophages (Kengatharan et al 1996a,b). However, even if the end pathology may look the same in very broad terms, the signalling and sensing of LPS and LTA could not be more different.…”

Section: Tlr4 Versus Tlr2mentioning

confidence: 99%

Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease

Mitchell¹,

Paul-Clark²,

Clarke³

et al. 2007

Journal of Endocrinology

120

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Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line-encoded receptors, including transmembrane Toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine-rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular patterns (PAMPs) results in genomic responses in host cells involving activation transcription factors and the induction of genes. There are now at least 10 TLRs in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via interactions with adaptor proteins including MyD88 and tollreceptor associated activator of interferon (TRIF). NOD signalling is via the inflammasome and involves activation of Rip-like interactive clarp kinase (RICK). Bacterial lipopolysaccharide (LPS) from Gram-negative bacteria is the beststudied PAMP and is activated by or 'sensed' by TLR4. Lipoteichoic acid (LTA) from Gram-positive bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades, although activation of either results in symptoms of sepsis and shock. This review describes the rapidly expanding field of pathogen-sensing receptors and uses LPS and LTA as examples of how these pathways parallel and diverge from each other. The role of pathogen-sensing pathways in disease is also discussed.

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“…Staphylococcal LTA has been shown to induce the production of tumor necrosis factor alpha (TNF-␣) (9) and nitric oxide (NO) (7,22). It has also been shown to induce sepsis in rats when peptidoglycan is coadministered (8,23,26). Thus, staphylococcal LTA may be as important in causing gram-positive bacterial sepsis as LPS is in causing gram-negative bacterial sepsis.…”

mentioning

confidence: 99%

Monoacyl Lipoteichoic Acid from Pneumococci Stimulates Human Cells but Not Mouse Cells

Kim¹,

Seo

Han

et al. 2005

Infect Immun

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We have developed a method for obtaining pneumococcal lipoteichoic acid (LTA) with none, one, or two acyl chains. Anion-exchange chromatography at pH 9.5 yields pneumococcal LTA (labeled LTA-9.5) that has a mass spectrum identical to that of pre-ion-exchange LTA and loses 500 mass units after deacylation by alkali hydrolysis. Anion exchange at pH 10.5 produces LTA (labeled LTA-10.5) with mass peaks that are 264 mass units lower than those of pre-ion-exchange LTA, and deacylation of LTA-10.5 by alkali hydrolysis reduces the mass by only 239 mass units. This result indicates that LTA-10.5 has lost one of the two acyl chains, whereas LTA-9.5 has both acyl chains. When the biological properties of LTA-9.5 and LTA-10.5 are examined with mouse cells, only LTA-9.5 (and not LTA-10.5) is able to stimulate mouse cells to produce tumor necrosis factor alpha, interleukin-1␤, and nitric oxide. In contrast, both LTA-9.5 and LTA-10.5 can stimulate human cells. LTA became inactive when both acyl chains were removed. Thus, acyl chains are critical for LTA function, and small variations in acyl chains can alter biological properties of LTA.Lipoteichoic acid (LTA) is an important component of the cell walls of gram-positive bacteria. LTA is a polyphosphate polymer that is linked to a glycerol backbone with two acyl chains (10). The acyl chains anchor the molecule to the bacterial plasma membrane. The resulting LTA structure is amphipathic, which is also true of the lipopolysaccharide (LPS) of gram-negative bacteria. Also, like LPS, LTA is considered to be an important pathogen-associated molecular pattern capable of stimulating innate immunity and responsible for grampositive bacterial sepsis. However, the biological properties of LTA are only beginning to be elucidated because the LTA used in previous studies may have contained biologically active contaminants (12) or may have been altered in structure (25). The biological properties of LTA have been investigated mostly with staphylococcal LTA, which stimulates platelet-activating factor receptor (24) and TLR2 (9, 30). Staphylococcal LTA has been shown to induce the production of tumor necrosis factor alpha (TNF-␣) (9) and nitric oxide (NO) (7,22). It has also been shown to induce sepsis in rats when peptidoglycan is coadministered (8,23,26). Thus, staphylococcal LTA may be as important in causing gram-positive bacterial sepsis as LPS is in causing gram-negative bacterial sepsis.Along with staphylococci, pneumococci are responsible for most cases of gram-positive bacterial sepsis, which accounts for about half of all cases of bacterial sepsis (6, 35). Pneumococcal LTA has also been shown to stimulate cells via TLR2 (16,29). Yet to date, pneumococcal LTA has not been studied as extensively as has staphylococcal LTA. Also, it is difficult to extrapolate biological properties of staphylococcal LTA to those of pneumococcal LTA, since the two LTAs have significant structural differences. For instance, the polyphosphate polymer of staphylococcal LTA is composed of 20 to 50 small and va...

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Role of nitric oxide in the circulatory failure and organ injury in a rodent model of Gram‐positive shock

Cited by 95 publications

References 55 publications

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease

Monoacyl Lipoteichoic Acid from Pneumococci Stimulates Human Cells but Not Mouse Cells

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