Human Intestinal Ischemia-Reperfusion–Induced Inflammation Characterized
Open accessAbstract
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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Increased nitrate concentrations and an altered mucosal oxygen gradient favour the growth of microbes in the Proteobacteria phylum and some members of the Firmicutes phylum.
“Increased nitrate concentrations13 and an altered mucosal oxygen gradient29 favour the growth of microbes in the Proteobacteria phylum”
From The microbiome and critical illness (2016) · cites this paper as [16]
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References 42 · Cited by 186
Research works printed but not linked: 1
- Arrieta MC, Bistritz L, Meddings JB: Alterations in intestinal perme- ability. Gut 2006, 55:1512-1520
- Authors
- Grootjans, J., Lenaerts, K., Derikx, J. P. M., Matthijsen, R. A., de Bruïne, A. P., van Bijnen, A. A., van Dam, R. M., Dejong, C. H. C., & Buurman, W. A.
- Affiliations
- Maastricht University Medical Centre (NL)
- Zuyderland Medisch Centrum (NL)
- Spaarne Ziekenhuis (NL)
- Corresponding author
- Lenaerts, Kaatje
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 176
- Issue
- 5
- Pages
- 2283-2291
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2861093
- OpenAlex
- W1593435431
- Cited by
- 186
- References
- 42
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 8 · 2023: 16 · 2022: 13 · 2021: 14 · 2020: 9 · 2019: 14 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 13 · 2014: 11 · 2013: 16 · 2012: 8
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Universiteit Maastricht
- Maastricht Universitair Medisch Centrum
- Topics
- Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- intestinal ischemia-reperfusion injury, intestinal inflammation, human small intestine, intestinal barrier integrity, intestinal fatty acid binding protein, endotoxin, complement activation, C3c, interleukin-6, interleukin-8, TNF-α, ICAM-1, neutrophil influx, endothelial activation
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Inflammation, Intestine, Small, Male, Middle Aged, Tumor Necrosis Factor-alpha, Reperfusion Injury, Interleukin-6, Complement C3c, Interleukin-8, Tissue Culture Techniques
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