Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing

Autor: Charles A. Parkos, Anny-Claude Luissint, Hikaru Nishio, Jennifer C. Brazil, Dominique A. Weber, Andrew S. Neish, Asma Nusrat, Ronen Sumagin, Porfirio Nava, Ashfaqul Alam
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Colon
Neutrophils
Biopsy
Immunology
Cell Communication
Biology
Transepithelial Migration
Article
Cell Line
Tissue Culture Techniques
Mice
03 medical and health sciences
0302 clinical medicine
Intestinal mucosa
Cell surface receptor
medicine
Animals
Humans
Immunology and Allergy
Intestinal Mucosa
Immunity
Mucosal
Protein kinase B
beta Catenin
Cell Proliferation
Wound Healing
ICAM-1
Transendothelial and Transepithelial Migration
Epithelial Cells
Intercellular Adhesion Molecule-1
Epithelium
3. Good health
Cell biology
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
Signal transduction
Wound healing
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Mucosal immunology
ISSN: 1933-0219
Popis: A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.
Databáze: OpenAIRE
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