Neutrophil Migration Under Normal and Sepsis Conditions

Lerman, Yelena V.; Kim, Min‐Soo

doi:10.2174/1871529x15666150108113236

Cited by 80 publications

(83 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the link between the AQP5 -1364A/C polymorphism and sepsis survival could be due to AQP5 expression and its impact on neutrophil cell migration. Less cell migration can cause less tissue damage caused by infiltrating neutrophils and pro-inflammatory mediators [12, 24]. Another possible mechanism which was not examined in this study is the potential impact of AQP5 expression on neutrophil maturation.…”

Section: Discussionmentioning

confidence: 99%

“…To this end, a decreased AQP5 expression may decrease immune cell migration and may subsequently alter the inflammatory chain during sepsis. The migration of neutrophils is essential in immune response during sepsis [11] and its regulation is critical for sepsis outcome as sufficient neutrophil migration is critical for pathogen clearance but excessive neutrophil migration is associated tissue damage and subsequent organ dysfunction [12]. In addition regulation of AQP5 expression in neutrophils has not been studied yet and was therefore addressed with this study.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study

et al. 2016

View full text Add to dashboard Cite

BackgroundThe C-allele of the aquaporin (AQP5) -1364A/C polymorphism is associated with decreased AQP5 expression but increased 30-day survival in patients with severe sepsis. AQP5 expression might affect survival via an impact on cell migration. Consequently, we tested the hypothesis that (1) Aqp5 knockout (KO) compared to wild type (WT) mice show an increased survival following lipopolysaccharide (LPS) administration, and that (2) AQP5 expression and the AQP5 -1364A/C polymorphism alters immune cell migration.MethodsWe investigated Aqp5-KO and wild type mice after intraperitoneal injection of either E.coli lipopolysaccharide (LPS, serotype O127:B8, 20 mg/kg) or saline. Furthermore, neutrophils of volunteers with the AA-AQP5 or AC/CC-AQP5- genotype were incubated with 10−8 M Chemotactic peptide (fMLP) and their migration was assessed by a filter migration assay. Additionally, AQP5 expression after fMLP incubation was analyzed by RT-PCR and Western blot. Moreover, migration of AQP5 overexpressing Jurkat cells was studied after SDF-1α-stimulation. We used exact Wilcoxon–Mann–Whitney tests; exact Wilcoxon signed-rank tests and the Kaplan–Meier estimator for statistical analysis.ResultsFifty-six percent of Aqp5-KO but only 22% of WT mice survived following LPS-injection. WT mice showed increased neutrophil migration into peritoneum and lung compared to Aqp5-KO mice. Target-oriented migration of neutrophils was seen after 0.5 h in AA-genotype cells but only after 1.5 h in AC/CC-genotype cells, with a threefold lower migrating cell count. AQP5 overexpressing Jurkat cells showed a 2.4 times stronger migration compared to native Jurkat cells.ConclusionThe AQP5 genotype may influence survival following LPS by altering neutrophil cell migration. Trial registration DRKS00010437. Retrospectively registered 26 April 2016Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1079-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The intensity and duration of these responses are associated with increased secondary infections and mortality (Gotts and Matthay, 2016). It is well–established in animal models subjected to sepsis and by clinical evidence in humans that circulating neutrophils become activated, which impairs their migration to sites of infection and causes them to sequester in the vascular beds of organs where they promote vascular occlusions and leakage, and tissue destruction (Alves-Filho et al, 2010b; Sônego et al, 2014; Lerman and Kim, 2015). These are key events that promote multiple organ failure and septic shock.…”

Section: Neutrophil Dysfunction During Sepsismentioning

confidence: 99%

Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis

Mishra

Walcheck

2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

show abstract

“…[30] Impairment of neutrophil migration has been described in sepsis, suggesting that in human sepsis, failure of neutrophil migration is associated with a poor prognosis. [31] The mechanism involved in the impairment of neutrophil migration is still elusive.…”

Section: Neutrophil Dysfunction In Sepsismentioning

confidence: 99%

Neutrophil Dysfunction in Sepsis

Zhang

Liu

Gao

et al. 2016

Chinese Medical Journal

View full text Add to dashboard Cite

Objective:Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis.Data Sources:Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”.Study Selection:Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis.Results:We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis.Conclusions:Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed.

show abstract

Neutrophil Migration Under Normal and Sepsis Conditions

Cited by 80 publications

References 130 publications

AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study

AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study

Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis

Neutrophil Dysfunction in Sepsis

Contact Info

Product

Resources

About