Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti‐inflammatory and antimicrobial effects in murine pneumococcal pneumonia

Boogaard, Florry E. van den; Brands, Xanthe; Schultz, Marcus J.; Levi, Marcel; Roelofs, Joris J. T. H.; Veer, Cornelis van ’t; Poll, Tom van der

doi:10.1111/j.1538-7836.2010.04089.x

Cited by 44 publications

(53 citation statements)

References 41 publications

(106 reference statements)

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“…However, no consensus has been reached with respect to dose volume for delivery to the LRT. A random survey of very recently published papers in which intranasal instillation was employed for delivery of infectious agents (bacterial and fungal pathogens) to the lungs of mice revealed that researchers used a wide range of dose volumes in combination with a variety of anesthesia types as follows: i) 20 µl instillation volume under pentobarbital [28] or ketamine/xylazine anesthesia [29], [30], [31], [32], [33], ii) 25 µl instillation volume under either pentobarbital [34] or ketamine/xylazine anesthesia [35], iii) 30 µl instillation volume under ketamine/xylazine anesthesia [36], iv) 35 µl instillation volume under ketamine/xylazine anesthesia [37], v) 40 µl instillation volume under isoflurane anesthesia [38], vi) 50 µl instillation volume under either ketamine/xylazine [39], isoflurane [40], [41], [42], [43], [44], halothane [45], [46], and vii) 100 µl instillation volume under isoflurane anesthesia [47]. Moreover, a number of recent papers either supplied information regarding the dose volume used without indicating the type of anesthesia [48], [49], indicated the anesthesia used but failed to indicate the dose volume [50], [51], or supplied no information regarding either the dose volume or anesthesia [52], [53], [54] used for intranasal instillation.…”

Section: Discussionmentioning

confidence: 99%

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

et al. 2012

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Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

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Section: Discussionmentioning

confidence: 99%

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

et al. 2012

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“…Thus, using regulatory coagulation proteins for infection treatment is a possible therapeutic approach, previously explored in infection models and clinical trials employing various modulatory proteins, such as the serpin antithrombin III [9], recombinant tissue factor pathway inhibitor 1 [10]–[12] or recombinant activated protein C [13]. Unfortunately, none of the above was successful [9], [13], [14], indicating a need for new anti-infective drugs.…”

Section: Introductionmentioning

confidence: 99%

A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection

et al. 2014

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Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

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“…We were interested in determining the effect of R-roscovitine on an already ongoing and increasing inflammatory response in the lung elicited by a grampositive stimulus. For this step, we chose our established model of gram-positive pneumonia in which mice are first challenged with a high dose of the clinically relevant respiratory pathogen S. pneumoniae and treated 24 h later with ceftriaxone (24,30). For the purpose of this study, ceftriaxone treatment was given 24 and 72 h after infection and combined with either R-roscovitine or vehicle.…”

Section: R-roscovitine Treatment Lowers Pmn Counts In Bal Fluid Durinmentioning

confidence: 99%

R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

Hoogendijk

Roelofs

Duitman

et al. 2012

Mol Med

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Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) is an important proinflammatory component of the gram-positive bacterial cell wall. R-roscovitine, a purine analog, is a potent cyclin-dependent kinase (CDK)-1, -2, -5 and -7 inhibitor that has the ability to inhibit the cell cycle and to induce polymorphonuclear cell (PMN) apoptosis. We sought to investigate the effect of R-roscovitine on LTA-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LTA or viable S. pneumoniae in vivo. In vitro R-roscovitine enhanced apoptosis in PMNs and reduced tumor necrosis factor (TNF)-α and keratinocyte chemoattractant (KC) production in MH-S (alveolar macrophage) and MLE-12/ MLE-15 (respiratory epithelial) cell lines. In vivo R-roscovitine treatment reduced PMN numbers in bronchoalveolar lavage fluid during LTA-induced lung inflammation; this effect was reversed by inhibiting apoptosis. Postponed treatment with R-roscovitine (24 and 72 h) diminished PMN numbers in lung tissue during gram-positive pneumonia; this step was associated with a transient increase in pulmonary bacterial loads. R-roscovitine inhibits proinflammatory responses induced by the gram-positive stimuli LTA and S. pneumoniae. R-roscovitine reduces PMN numbers in lungs upon LTA administration by enhancing apoptosis. The reduction in PMN numbers caused by R-roscovitine during S. pneumoniae pneumonia may hamper antibacterial defense.

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Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti‐inflammatory and antimicrobial effects in murine pneumococcal pneumonia

Abstract: Therapeutic rh-TFPI attenuates coagulation, inflammation and bacterial growth during pneumococcal pneumonia, whereby the latter two effects only become apparent in the absence of concurrent antibiotic treatment.

Cited by 44 publications

References 41 publications

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection

R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

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