Human intestinal ischemia-reperfusion-induced inflammation characterized: experiences from a new translational model.

J. Grootjans, K. Lenaerts, J.P. Derikx, R.A. Matthijsen, A.P. de Bruine, A.A. van Bijnen, R.M. van Dam, C.H.C. Dejong, W.A. Buurman

Research output: Contribution to journalArticleAcademicpeer-review

62 Citations (Scopus)

Abstract

Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.
Original languageEnglish
Pages (from-to)2283-2291
Number of pages9
JournalAmerican Journal of Pathology
Volume176
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • ISCHEMIA/REPERFUSION INJURY
  • SYSTEMIC INFLAMMATION
  • COMPLEMENT PATHWAY
  • ORGAN DYSFUNCTION
  • GUT ISCHEMIA
  • DAMAGE
  • INHIBITION
  • LEUKOCYTE
  • RAT
  • INVOLVEMENT

Cite this

Grootjans, J. ; Lenaerts, K. ; Derikx, J.P. ; Matthijsen, R.A. ; de Bruine, A.P. ; van Bijnen, A.A. ; van Dam, R.M. ; Dejong, C.H.C. ; Buurman, W.A. / Human intestinal ischemia-reperfusion-induced inflammation characterized: experiences from a new translational model. In: American Journal of Pathology. 2010 ; Vol. 176, No. 5. pp. 2283-2291.
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abstract = "Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.",
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Human intestinal ischemia-reperfusion-induced inflammation characterized: experiences from a new translational model. / Grootjans, J.; Lenaerts, K.; Derikx, J.P.; Matthijsen, R.A.; de Bruine, A.P.; van Bijnen, A.A.; van Dam, R.M.; Dejong, C.H.C.; Buurman, W.A.

In: American Journal of Pathology, Vol. 176, No. 5, 05.2010, p. 2283-2291.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Lenaerts, K.

AU - Derikx, J.P.

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AU - de Bruine, A.P.

AU - van Bijnen, A.A.

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AU - Buurman, W.A.

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N2 - Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.

AB - Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.

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KW - SYSTEMIC INFLAMMATION

KW - COMPLEMENT PATHWAY

KW - ORGAN DYSFUNCTION

KW - GUT ISCHEMIA

KW - DAMAGE

KW - INHIBITION

KW - LEUKOCYTE

KW - RAT

KW - INVOLVEMENT

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DO - 10.2353/ajpath.2010.091069

M3 - Article

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SP - 2283

EP - 2291

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

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ER -