Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis

Zeerleder, Sacha; Caliezi, Christoph; Mierlo, Gerard van; Eerenberg-Belmer, A.J.M.; Sulzer, Irmela; Hack, C. E.; Wuillemin, Walter A.

doi:10.1128/cdli.10.4.529-535.2003

Cited by 59 publications

(42 citation statements)

References 55 publications

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“…Moreover, VncS senses LF in the blood and induces the vncRS operon and subsequent lysis. The initial incoming signal, LF, the presence of which in the blood is strongly correlated to the occurrence of sepsis [34–36], was found to play a crucial role in lysis, albeit only a small percentage (<1%) of the bacterial population was lysed (Suppl Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

et al. 2018

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Streptococcus pneumoniae (pneumococcus), the major pathogen for pneumonia, commonly colonizes the lung, but the mechanism underlying the coordination of virulence factors during invasion via the host protein remains poorly understood. Bacterial lysis releases the components of the cell wall, and triggers innate immunity and the subsequent secretion of pro-inflammatory cytokines. Previously, the virulence of the pep27 mutant was shown to be attenuated as a feasible candidate for vaccine development. However, the role of pep27 gene, belonging to the vancomycin-resistance locus (vncRS operon), in virulence, is largely unknown. This study demonstrates that transferrin in the host serum reduces the survival of the host during S. pneumoniae infections in mice. The exposure of the pneumococcal D39 strain to lactoferrin induced the vncRS operon, lysis, and subsequent in vivo cytokine production, resulting in lung inflammation. However, these responses were significantly attenuated in pneumococci harboring a mutation in pep27. Mechanistically, the VncS ligand, identified as lactoferrin, induced the vncRS operon and increased the in vivo mortality rates. Thus, serum-induced activation of vncRS plays an essential role in inducing pneumonia.

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Section: Discussionmentioning

confidence: 99%

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

et al. 2018

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“…This partially explains the increased levels of nucleosomes and EA complexes that were also found in our controls, contrary to other studies that assessed levels in a control group. 5,17,19,20 Although significantly increased levels of circulating nucleosomes and EA complexes were demonstrated in patients with DVT, their origin and role are still unclear. Levels of circulating nucleosomes in DVT patients may reflect the degradation of NETs in the thrombus but could also derive from other cell sources within or outside the thrombus.…”

Section: Discussionmentioning

confidence: 99%

Circulating Nucleosomes and Neutrophil Activation as Risk Factors for Deep Vein Thrombosis

Montfoort

Stephan

Lauw

et al. 2013

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Objective-The formation of neutrophil extracellular traps and the exposure of nucleosomes on these neutrophil extracellular traps contribute to coagulation activation and the propagation of deep vein thrombosis (DVT) in animal models. However, no data are available on the role of neutrophil extracellular traps or nucleosomes in patients with thrombosis. Methods and Results-We conducted a case-control study, in which levels of circulating nucleosomes and neutrophil elastase-α1-antitrypsin complexes were assessed in plasma from 150 patients with objectified symptomatic DVT (cases) and compared with 195 patients with a clinical suspicion of DVT but in whom DVT was excluded (controls). We explored the association between both nucleosomes and elastase-α1-antitrypsin complexes, and the presence of DVT by calculating the odds ratio with corresponding 95% CIs. Elevated levels of both circulating nucleosomes and elastase-α1-antitrypsin complexes were associated with a 3-fold risk of DVT, and the associations remained similar after adjustment for potential confounders (malignancy, smoking, recent immobilization, recent hospitalization). The risk increased with higher nucleosome and elastase-α1-antitrypsin complex levels, suggesting a dose-dependent relationship among circulating nucleosomes, activated neutrophils, and DVT. Conclusion-Our study suggests an association among circulating nucleosomes, activated neutrophils, and presence of DVT in humans, which might have implications for treatment and prevention.

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“…However there was no relationship between either complement activation or neutrophil elastase and postoperative liver function tests. Such a relationship has previously been described both in sepsis 14 and reperfusion injury. 15,16 This is likely to reflect the small sample size and the population heterogeneity rather than a lack of association between preservation injury, immune activation and subsequent graft damage and function.…”

Section: Discussionmentioning

confidence: 78%

Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation

et al. 2004

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on behalf of the Leeds Liver GroupHemodynamic changes and elevation of intracellular calcium following reperfusion in human liver transplantation occur rapidly and do not match the time course of cytokine expression, therefore, we postulate involvement of other, pre-formed substances, such as complement. We studied 40 adult patients undergoing liver transplantation. Blood was drawn for estimation of C3, C4, C3 degradation product, membrane attack complex, and CH100 levels and elastase (a marker of neutrophil activation) at induction of anesthesia, 5 minutes before reperfusion, 5 minutes and 60 minutes after reperfusion. Cardiac output was measured by thermodilution and systemic vascular resistance was calculated at these same time points. There was a significant rise in C5b-9 membrane attack complex (P ‫؍‬ .0012) with a corresponding fall in C3 (P ‫؍‬ .0013) and C4 (P ‫؍‬ .0002) levels and a rise in C3 degradation product levels (P ‫؍‬ .0006). There was no significant change in CH100. These changes very closely followed the hemodynamic changes of a significant fall in systemic vascular resistance index (P ‫؍‬ .0024) and increase in cardiac index (P ‫؍‬ .0005). Elastase rose from 356 ؎ 53 to 557 ؎ 40 g/L (P < .0001). There is complement activation and neutrophil activation at reperfusion in liver transplantation. Dilution alone cannot explain the fall in C3 and C4 levels as there is a corresponding increase in membrane attack complex and C3 degradation product levels with time. As both C3 and C4 are consumed, the classical pathway must be active, though alternative and lectin activated pathways may also be involved. These findings may, at least in part, explain the hemodynamic changes typically seen at reperfusion in liver transplantation. (Liver Transpl 2004;10:273-278.)

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Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis

Cited by 59 publications

References 55 publications

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

Circulating Nucleosomes and Neutrophil Activation as Risk Factors for Deep Vein Thrombosis

Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation

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