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Cited by 187Inflammatory Bowel DiseaseOcular Diseases and Behçet’s SyndromeCell Adhesion Molecules Research

Aggravation of Different Types of Experimental Colitis by Depletion or Adhesion Blockade of Neutrophils

Kühl, Anja A., Kakirman, Hacer, Janotta, Markus, Dreher, Stefan, Cremer, Philipp, Pawlowski, Nina N., Loddenkemper, Christoph, Heimesaat, Markus M. +4 more·2007·Gastroenterology
DOI 10.1053/j.gastro.2007.08.073
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Abstract

Background & aims Neutrophils are generally thought to play an important proinflammatory role in the pathogenesis of inflammatory bowel disease. The objective of this study was to evaluate whether blocking the invasion of neutrophils by anti-L-selectin monoclonal antibodies modulates chemically induced colitis and how this modulation is accomplished.Methods Trinitrobenzene sulfonic acid/dinitrobenzene sulfonic acid (TNBS/DNBS)-induced colitis was studied in rats on treatment with anti-L-selectin monoclonal antibodies (mAb) or antineutrophil antiserum. Different anti-L-selectin mAb, either blocking or nonblocking, as well as F(ab)(2) fragments were evaluated. Additionally, leukocyte migration was examined using intravital microscopy. Furthermore, the effect of neutrophil depletion in rat TNBS-induced colitis was studied either prior to or after colitis induction as well as murine CD4(+)CD45RB(high) transfer colitis. Finally, bacterial translocation during DNBS-induced colitis was studied in neutrophil-depleted and control rats.Results Anti-L-selectin mAb treatment resulted in increased mortality and bowel inflammation as well as hemorrhagic eye secretion. No clear difference was found between blocking and nonblocking mAb or F(ab)(2) fragments. For all investigated antibodies/fragments, either complete blockade of leukocyte invasion or marked neutrophil depletion was found. Accordingly, neutrophil depletion by antiserum resulted in aggravation of rat DNBS-induced colitis as well as murine transfer colitis.Conclusions Adhesion blockade or neutrophil depletion aggravates rat TNBS/DNBS-induced colitis together with extraintestinal manifestations of the eyes. Therefore, neutrophils appear to have an important role in mucosal repair processes. Importantly, adhesion blockade as a therapeutic concept can be detrimental in inflammatory bowel disease.

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Crossref · 10.1053/j.gastro.2007.08.073

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  • A recent study used PMN depletion techniques to document a central role for PMN in the resolution of inflammation in several murine IBD models.

    “A recent study, for example, used PMN depletion techniques to document a central role for PMN in the resolution of inflammation in several murine IBD models36.”

    From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [36]

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Authors
Kühl, A. A., Kakirman, H., Janotta, M., Dreher, S., Cremer, P., Pawlowski, N. N., Loddenkemper, C., Heimesaat, M. M., Grollich, K., Zeitz, M., Farkas, S., & Hoffmann, J. C.
Affiliations
  • Charité – Universitätsmedizin Berlin (DE)
  • Universitätsklinikum des Saarlandes (DE)
  • University of Regensburg (DE)
Corresponding author
Hoffmann, Jörg C.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2007-12
Volume
133
Issue
6
Pages
1882-1892
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2007.08.073
OpenAlex
W2135824704
Cited by
187
References
58
Citations by year
2026: 7 · 2025: 7 · 2024: 10 · 2023: 12 · 2022: 10 · 2021: 14 · 2020: 7 · 2019: 10 · 2018: 12 · 2017: 11 · 2016: 13 · 2015: 15 · 2014: 11 · 2013: 8 · 2012: 9
FWCI
4.11
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
neutrophils, L-selectin, neutrophil depletion, chemically induced colitis, bacterial translocation, leukocyte migration, mucosal healing, inflammatory bowel disease, extraintestinal manifestations
MeSH terms
Animals, Antibodies, Monoclonal, Cell Adhesion, Cell Migration Inhibition, Chemotaxis, Leukocyte, Colitis, Disease Models, Animal, Female, Intestinal Mucosa, Neutrophils, Rats, Inbred Lew, Rats

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