Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation

Bijuklic, Klaudija; Jennings, Paul; Kountchev, Jordan; Haßlacher, Julia; Aydin, Sonia; Sturn, Daniel H.; Pfaller, Walter; Patsch, Josef R.; Joannidis, Michael

doi:10.1152/ajpcell.00419.2006

Cited by 46 publications

(41 citation statements)

References 28 publications

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“…Thus, IgG bound to uromodulin significantly enhances neutrophil migration. LLC-PK1 monolayers were also pre-incubated with LPS in order to simulate an inflamed tissue as previously described [24,26]. Uromodulin expressing cells showed a larger LPS response than non expressing cells (4.43 fold ± 1.41, P = 0.0047) (Fig.…”

Section: Uromodulin Facilitates Pmn Migrationmentioning

confidence: 96%

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Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Schmid

Prajczer

Grüber

et al. 2010

Cell Physiol Biochem

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The glycosylated protein uromodulin is exclusively found in the thick ascending limb cells (TAL) of the kidney, where it is produced on mass and apically targeted, eventually being secreted into the urine. Recently, there has been a renewed interest in this protein due to its ability to interact with the immune system, implicating this protein as a renal inflammatory molecule. Here we investigated the potential role of membrane bound uromodulin on neutrophil adhesion and trans-epithelial migration. The renal tubular epithelial cell line, LLC-PK1, stably transfected with human uromodulin was used to investigate the influence of uromodulin on neutrophil adherence and migration. Uromodulin expression resulted in a significant increase of neutrophil adherence and trans-epithelial migration, in both the apical to basolateral and the basolateral to apical direction. Although uromodulin is GPI anchored and targeted to the apical membrane, we could also observe expression in the basal and lateral membranes domains, which may be responsible for basolateral to apical migration. Furthermore we show that uromodulin binds both the heavy and light chain of IgG, and that IgG enhances neutrophil migration. This study demonstrates that uromodulin can facilitate neutrophil trans-epithelial migration and that this migration can be amplified by co-factors such as IgG.

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Section: Uromodulin Facilitates Pmn Migrationmentioning

confidence: 96%

“…In this study, using a trans-epithelial neutrophil migration assay previously described [23][24][25], we investigated the epithelial expression of uromodulin on neutrophil migration. We demonstrate for the first time that uromodulin expression facilitates neutrophil trans-epithelial migration.…”

Section: Introductionmentioning

confidence: 99%

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Schmid

Prajczer

Grüber

et al. 2010

Cell Physiol Biochem

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“…The onset and progression of impaired renal function is based on a defective interplay between the tubular and vascular renal compartments. To investigate these complex interactions, we recently established a co-culture model composed of human endothelialcells and human renal proximal tubular cells cultured on opposite sides of polycarbonate growth membranes, which mimics the renal interstitial situation [16,17].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of NO Inhibition in Renal Epithelial and Endothelial Cells in Mono-Culture vs. Co-Culture Conditions

Bertocchi¹,

Schmid²,

Haßlacher³

et al. 2010

Cell Physiol Biochem

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Nitric oxide (NO) plays a critical role in the regulation of renal hemodynamics and tubular function after post-ischemic damage or sepsis. Diminished NO bioavailability contributes to endothelial dysfunction and may be caused by reduced NO synthesis due to substrate or co-factor deficiency. The aim of this study was to investigate the effects of NOS inhibition and NO depletion in a renal endo-epithelial bilayer model compared to monolayers of proximal tubular epithelial (HK-2) cells and endothelial cells of venous origin (EA.hy 926) with respect to cellular integrity, apoptosis and cytokine release. Two different NOS inhibitors have been used: an arginine-based-inhibitor, L-N^Gmonomethyl-arginine (L-NMMA) and a cofactor-based-inhibitor, H4-amino-biopterin (4-ABH₄) showing iNOS selectivity. We found significantly higher basal NO production by epithelial than by endothelial monolayers, which was significantly reduced by both NOS-inhibitors with a stronger effect demonstrated by 4-ABH₄. Furthermore we detected significant basal iNOS protein expression in unstimulated HK-2 cells. NOS inhibition by 4-ABH₄ was associated with increased LDH release, apoptosis and reduced IL-6 production in epithelial but not in endothelial monolayers. These effects on epithelial cells were abolished under co-culture conditions. In contrast, endothelial cells showed higher IL-6 and IL-8 release under co-culture conditions than in monolayers, with IL-8 production being largely suppressed by L-NMMA but not by 4-ABH₄. In conclusion, inhibition of basal NO production in epithelial monolayers shows detrimental effects on cell integrity and viability. Under co-culture conditions interrelation between epithelial and endothelial cells appears to counteract these potentially harmful effects of epithelial NOS inhibition.

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“…Ancak, birçok ABH olan hastada daha sonra sepsis gelişmesinin, ABH olanlarda bir immünopa-ralizi durumunu soru işareti olarak belirlemiştir. ABH'de immün fonksiyonların bozukluğunu açıklayan birkaç çalışmadan söz edersek; kronik üreminin sekonder immün hasar yaratması (16) , eritropoetin hormonunun immunomodülatuvar etkisi (17) , renal tubuler hücrelerin stres durumunda immün düzenleyici görevleri (18) gibi örnekler verilebilir.…”

Section: Discussionunclassified

Prognostic Effects of RIFLE Criteria on Mortality and Morbidity in Septic Patients with Acute Kidney Injury

Şentürk¹,

Soydan²,

Özcan³

et al. 2012

J Turk Anaesth Int Care

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ÖZETAmaç: Sepsis ve septik şok sıklıkla akut böbrek hasarı (ABH) ile birlikte seyreder ve kombinasyonunda mortalite %60'a kadar yükselebilir. Bu çalışmada kritik hastalarda ve sepsiste böbrek yetersizliğinin risk (R), böbrek hasarı (I), böbrek fonksiyonunda yetersizlik (F), böbrek fonksiyonun kaybı (L) ve son dönem böbrek yetersizliği (E) (RIFLE) sınıf-landırmasına göre sağkalımı araştırılmıştır. Sonuç: RIFLE sınıflaması hastane içi mortalite ve kısa dönem prognoz ile ilgili olarak yoğun bakımdaki sepsisli hastalarda bir öngörü sağlayabilmektedir.Anahtar kelimeler: Akut böbrek yetersizliği, RİFLE sınıflaması, sağkalım SUMMARY Prognostic Effects of RIFLE Criteria on Mortality and Morbidity in Septic Patients with Acute Kidney InjuryObjective: Sepsis and septic shock are often complicated by acute kidney injury (ABH), and the mortality rates can be as high as 60 % in their combination. This study investigates the outcomes of critically ill and septic patients, and elucidates the association between prognosis and risk of renal failure (R), injury to the kidney (I), failure of the renal function (F), loss of kidney function (L), and end-stage renal failure (E) (RIFLE) classification.Material and Methods: After the approval of ethics committee 1140 patients admitted in our University hospital ICU from January 2007 until December 2007, were retrospectively evaluated. Patients with renal failure or renal transplants were excluded. Clinical, and laboratory parameters related to renal failure, sepsis and survival rates of the patients were evaluated.Results: Among 1031 patients, 15.6 % (n=161) have ABH according to RIFLE classification in the first 24 hours. Patients were classified as those with sepsis 53.41 % (n=86) and without sepsis-ABH 46.59 % (n=75). Although patients with only ABH had a mortality rate of 28 %, patients that have sepsis and ABH; had a mortality rate of 55.8 %. The severity of the disease according to RIFLE classification correlated with Acute Physiology and Chronic Health Evaluation (APACHE II) and sequential organ failure assessment scores.Conclusion: These findings are consistent with a role for RIFLE classification in accurately predicting in-hospital mortality and short-term prognosis in ICU patients with sepsis.

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Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation

Cited by 46 publications

References 28 publications

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Differential Effects of NO Inhibition in Renal Epithelial and Endothelial Cells in Mono-Culture vs. Co-Culture Conditions

Prognostic Effects of RIFLE Criteria on Mortality and Morbidity in Septic Patients with Acute Kidney Injury

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