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Morphological and Compositional Analysis of Neutrophil Extracellular Traps Induced by Microbial and Chemical Stimuli
Published on: November 4, 2022
Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies
Tue Bjerg Bennike1, Thomas Gelsing Carlsen, Torkell Ellingsen
1*Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; †Organ Center, Hospital of Southern Jutland, Aabenraa, Denmark; ‡Institute of Regional Health Research-Center Soenderjylland, University of Southern Denmark, Odense, Denmark; §Department of Rheumatology, Odense University Hospital, Odense, Denmark; ‖Diagnostic Center, Section of Gastroenterology, Regional Hospital Silkeborg, Silkeborg, Denmark; ¶University Research Clinic for Innovative Patient Pathways, Aarhus University, Aarhus, Denmark; **Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; ††Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; ‡‡Department of Biomedicine, Aarhus University, Aarhus, Denmark; and §§Department of Internal Medicine, Regional Hospital Viborg, Viborg, Denmark.
Background:
The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology.
Methods:
Mucosal colon biopsies were taken by endoscopy from noninflamed tissue of 10 patients with UC and 10 controls. The biopsies were either snap-frozen for protein analysis or prepared for histology. The protein content of the biopsies was characterized by high-throughput gel-free quantitative proteomics, and biopsy histology was analyzed by light microscopy and confocal microscopy.
Results:
We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed.
Conclusions:
Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate immunity are all increased in abundance in the morphologically normal colon mucosa from patients with UC. The increased abundance of these antimicrobial compounds points to the stimulation of the innate immune system in the etiology of UC.
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