Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system
| Autor: | E. Michael Danielsen, Alba De Haro Hernando, Jørgen Olsen, Mohammad Yassin, Elisabeth M. Danielsen, Gert H. Hansen, Karina Rasmussen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Histology Colon Swine animal diseases Pharmacology Organ culture Biochemistry digestive system Permeability Mice 03 medical and health sciences dextran sulfate sodium (DSS)-induced colitis Organ Culture Techniques 0302 clinical medicine Animal model medicine Animals Colitis Dextran Sulfate Sodium colon organ culture Chemistry Dextran Sulfate Inflammatory Bowel Diseases Cell Biology medicine.disease inflammatory bowel disease (IBD) digestive system diseases carbohydrates (lipids) stomatognathic diseases 030104 developmental biology Permeability (electromagnetism) Female Permeability barrier 030217 neurology & neurosurgery Research Article Research Paper |
| Zdroj: | Danielsen, E M, De Haro Hernando, A, Yassin, M, Rasmussen, K, Olsen, J, Hansen, G H & Danielsen, E M 2020, ' Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system ', Tissue Barriers, vol. 8, no. 2, 1728165 . https://doi.org/10.1080/21688370.2020.1728165 Tissue Barriers article-version (VoR) Version of Record |
| Popis: | Dextran sulfate sodium (DSS)-induced colitis is the most commonly used animal model for inflammatory bowel diseases. However, the precise molecular action of DSS, in particular its initial effect on the epithelial tissue permeability, is still poorly understood. In the present work, organ culture of mouse – and pig colon explants were performed for 1–2 h in the presence/absence of 2% DSS together with polar- and lipophilic fluorescent probes. Probe permeability was subsequently assessed by fluorescence microscopy. DSS rapidly increased paracellular permeability of 70-kDa dextran without otherwise affecting the overall epithelial integrity. FITC-conjugated DSS likewise permeated the epithelial barrier and strongly accumulated in nuclei of cells scattered in the lamina propria. By immunolabeling, plasma cells, T cells, macrophages, mast cells, and fibroblasts were identified as possible targets for DSS, indicating that accumulation of the polyanion in nuclei was not confined to a particular type of cell in the lamina propria. In contrast, colonocytes were rarely targeted by DSS, but as visualized by transmission electron microscopy, it induced the formation of vacuole-like structures in the intercellular space between adjacent epithelial cells. Nuclei of various cell types in the lamina propria, including both cells of the innate and adaptive immune system, are novel targets for a rapid action of DSS, and from previous in vitro studies, polyanions like DSS are known to disrupt nucleosomes by binding to the histones. We therefore propose that nuclear targeting is one way whereby DSS exerts its inflammatory action as a colitogen in animal models of inflammatory bowel diseases. |
| Databáze: | OpenAIRE |
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