Human neutrophil–pulmonary microvascular endothelial cell interactions in vitro: Differential effects of nitric oxide vs. peroxynitrite

Shelton, Jennifer L.; Wang, Lefeng; Cepinskas, Gediminas; Inculet, Richard; Mehta, Sanjay

doi:10.1016/j.mvr.2008.06.001

Cited by 20 publications

(13 citation statements)

References 53 publications

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“…(18) Although the concentration of IL-6 and TNF-α were small (ng) in our model, other investigators have demonstrated alterations in neutrophil biology at similar concentrations. (19)…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism for neutrophil priming in trauma: Potential role of peritoneal fluid

Shah¹,

Jiménez²,

Walker³

et al. 2010

Surgery

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“…(18) Although the concentration of IL-6 and TNF-α were small (ng) in our model, other investigators have demonstrated alterations in neutrophil biology at similar concentrations. (19)…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism for neutrophil priming in trauma: Potential role of peritoneal fluid

Shah¹,

Jiménez²,

Walker³

et al. 2010

Surgery

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“…8,16,30,55,76,77 Studies suggest that activated neutrophils also independently promote endothelial dysfunction and contribute to barrier dysfunction. [78][79][80] The direct activation of endothelial TLR2 or TLR4 by bacterial lipopeptides or LPS, respectively, increases endothelial permeability. 8,16,30,55 In contrast, TLR9 agonists induce endothelial permeability in a neutrophil-dependent fashion.…”

Section: Endothelial Innate Immune Pathways In Sepsis-induced Endothementioning

confidence: 99%

Vascular endothelial cell Toll-like receptor pathways in sepsis

2015

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The endothelium forms a vast network that dynamically regulates vascular barrier function, coagulation pathways and vasomotor tone. Microvascular endothelial cells are uniquely situated to play key roles during infection and injury, owing to their widespread distribution throughout the body and their constant interaction with circulating blood. While not viewed as classical immune cells, endothelial cells express innate immune receptors, including the Toll-like receptors (TLRs), which activate intracellular inflammatory pathways mediated through NF-κB and the MAP kinases. TLR agonists, including LPS and bacterial lipopeptides, directly upregulate microvascular endothelial cell expression of inflammatory mediators. Intriguingly, TLR activation also modulates microvascular endothelial cell permeability and the expression of coagulation pathway intermediaries. Microvascular thrombi have been hypothesized to trap microorganisms thereby limiting the spread of infection. However, dysregulated activation of endothelial inflammatory pathways is also believed to lead to coagulopathy and increased vascular permeability, which together promote sepsis-induced organ failure. This article reviews vascular endothelial cell innate immune pathways mediated through the TLRs as they pertain to sepsis, highlighting links between TLRs and coagulation and permeability pathways, and their role in healthy and pathologic responses to infection and sepsis.

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“…Neutrophils play a crucial role in the ALI inflammatory response, which is predominantly mediated through iNOS induction and nitric oxide (NO)/peroxynitrite (ONOO − ) generation [2, 3]. Zymosan is a substance derived from the cell walls of the yeast Saccharomyces cerevisiae [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

Wang

Wang³

et al. 2016

Oncotarget

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Neutrophil release of NO/ONOO− induces endothelial cell barrier dysfunction in inflammatory acute lung injury (ALI). Previous studies using zymosan-triggered inflammation and ALI model revealed that zymosan promotes inducible NO synthase (iNOS) expression in neutrophils, and that isoflurane inhibits zymosan-induced oxidative stress and iNOS biosynthesis. However, the underlying mechanisms remain largely unknown. We found here that in zymosan-primed neutrophils, iNOS is transcriptionally activated by NF-κB, whose nuclear translocation is triggered by excessive reactive oxygen species (ROS) and consequently activated p38 MAPK. ROS production is attributed to zymosan-initiated Toll-like receptor 2 (TLR2) signaling, in which the adaptor MyD88 recruits and activates c-Src, and c-Src activates NADPH oxidase to generate ROS. Subanesthetic isoflurane counteracts the aforementioned zymosan-induced signaling by targeting N-methyl-D-aspartic acid (NMDA) glutamate receptor and thereby suppressing calcium influx and c-Src activation. Whereas iNOS accelerates NO/ONOO− production in neutrophils which eventually promote protein leak from pulmonary microvascular endothelial cells (PMVEC), isoflurane reduced NO/ONOO− release from zymosan-treated neutrophils, and thus relieves trans- PMVEC protein leak. This study provides novel insights into the roles of neutrophils and the underlying mechanisms in zymosan-induced ALI, and has implications for the therapeutic potential of subanesthetic isoflurane in attenuating inflammatory responses causing lung endothelial cell damage.

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Human neutrophil–pulmonary microvascular endothelial cell interactions in vitro: Differential effects of nitric oxide vs. peroxynitrite

Cited by 20 publications

References 53 publications

A novel mechanism for neutrophil priming in trauma: Potential role of peritoneal fluid

A novel mechanism for neutrophil priming in trauma: Potential role of peritoneal fluid

Vascular endothelial cell Toll-like receptor pathways in sepsis

Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

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