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Enterocyte shedding and epithelial lining repair following ischemia of the human small intestine attenuate inflammation.

Matthijsen RA, Derikx JP, Kuipers D, van Dam RM, Dejong CH, Buurman WA - PLoS ONE (2009)

Bottom Line: Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter.In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response.This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, School for Nutrition & Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands.

ABSTRACT

Background: Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut.

Methods and findings: Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (+/-11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy). HIF-1alpha gene expression doubled (p = 0.02) and C3 gene expression increased 4-fold (p = 0.01) over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p = 0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFalpha release, increased numbers of inflammatory cells (p = 0.71) or complement activation, assessed as activated C3 (p = 0.14), were detected in the reperfused tissue.

Conclusions: In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

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Tissue response to IR.Illustrative of rapid gut barrier repair, no translocation of LPS could be detected during the IR procedure. Translocation of LPS was calculated from arteriovenous differences in LPS plasma levels across the isolated bowel segment during reperfusion (Δ (V–A). p = 0.18).
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pone-0007045-g003: Tissue response to IR.Illustrative of rapid gut barrier repair, no translocation of LPS could be detected during the IR procedure. Translocation of LPS was calculated from arteriovenous differences in LPS plasma levels across the isolated bowel segment during reperfusion (Δ (V–A). p = 0.18).

Mentions: Disruption of the gut barrier may lead to translocation of microbiota and pro-inflammatory microbial products, such as endotoxin associated with gram negative bacteria (lipopolysacharide (LPS)). Therefore we assessed the translocation of LPS following the rapid and temporary disruption of the epithelial lining in response to IR observed in our model.[1] LPS translocation from the intestinal lumen was assessed by measuring arterio-venous (AV) differences in LPS concentration across the jejunal segment, using the LAL-assay. Surprisingly, no translocation of LPS (p = 0.18, n = 28) was detected at any time point during reperfusion (Fig. 3). The temporary loss of gut wall integrity observed during reperfusion, which is induced by massive shedding of apoptotic epithelial cells, does not lead to the translocation of LPS.


Enterocyte shedding and epithelial lining repair following ischemia of the human small intestine attenuate inflammation.

Matthijsen RA, Derikx JP, Kuipers D, van Dam RM, Dejong CH, Buurman WA - PLoS ONE (2009)

Tissue response to IR.Illustrative of rapid gut barrier repair, no translocation of LPS could be detected during the IR procedure. Translocation of LPS was calculated from arteriovenous differences in LPS plasma levels across the isolated bowel segment during reperfusion (Δ (V–A). p = 0.18).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2737143&req=5

pone-0007045-g003: Tissue response to IR.Illustrative of rapid gut barrier repair, no translocation of LPS could be detected during the IR procedure. Translocation of LPS was calculated from arteriovenous differences in LPS plasma levels across the isolated bowel segment during reperfusion (Δ (V–A). p = 0.18).
Mentions: Disruption of the gut barrier may lead to translocation of microbiota and pro-inflammatory microbial products, such as endotoxin associated with gram negative bacteria (lipopolysacharide (LPS)). Therefore we assessed the translocation of LPS following the rapid and temporary disruption of the epithelial lining in response to IR observed in our model.[1] LPS translocation from the intestinal lumen was assessed by measuring arterio-venous (AV) differences in LPS concentration across the jejunal segment, using the LAL-assay. Surprisingly, no translocation of LPS (p = 0.18, n = 28) was detected at any time point during reperfusion (Fig. 3). The temporary loss of gut wall integrity observed during reperfusion, which is induced by massive shedding of apoptotic epithelial cells, does not lead to the translocation of LPS.

Bottom Line: Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter.In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response.This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, School for Nutrition & Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands.

ABSTRACT

Background: Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut.

Methods and findings: Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (+/-11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy). HIF-1alpha gene expression doubled (p = 0.02) and C3 gene expression increased 4-fold (p = 0.01) over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p = 0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFalpha release, increased numbers of inflammatory cells (p = 0.71) or complement activation, assessed as activated C3 (p = 0.14), were detected in the reperfused tissue.

Conclusions: In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

Show MeSH
Related in: MedlinePlus