TY - JOUR
T1 - Neutrophil extracellular trap density increases with increasing histopathological severity of Crohn's disease
AU - Schroder, Angie L.
AU - Chami, Belal
AU - Liu, Yuyang
AU - Doyle, Chloe M.
AU - El Kazzi, Mary
AU - Ahlenstiel, Golo
AU - Ahmad, Gulfam
AU - Pathma-Nathan, Nimalan
AU - Collins, Geoff
AU - Toh, James
AU - Harman, Andrew
AU - Byrne, Scott
AU - Ctercteko, Grahame
AU - Witting, Paul K.
N1 - Publisher Copyright:
© 2021 Crohn's & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Background: Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans. Methods: Human intestinal biopsies were collected from Crohn's disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score. Results: A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P <. 0001) and unaffected CD (P <. 0001), with transitional CD specimens also showing greater staining than controls (P <. 05) and unaffected CD (P <. 05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P <. 0001) and unaffected CD (P <. 0001) and was significantly higher in transitional CD than in controls (P <. 0001) and unaffected CD (P <. 0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P <. 05), unaffected CD (P <. 0001) and transitional CD (P <. 05), with transitional CD specimens showing greater staining than unaffected CD (P <. 01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment. Conclusion: These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.
AB - Background: Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans. Methods: Human intestinal biopsies were collected from Crohn's disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score. Results: A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P <. 0001) and unaffected CD (P <. 0001), with transitional CD specimens also showing greater staining than controls (P <. 05) and unaffected CD (P <. 05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P <. 0001) and unaffected CD (P <. 0001) and was significantly higher in transitional CD than in controls (P <. 0001) and unaffected CD (P <. 0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P <. 05), unaffected CD (P <. 0001) and transitional CD (P <. 05), with transitional CD specimens showing greater staining than unaffected CD (P <. 01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment. Conclusion: These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.
UR - https://hdl.handle.net/1959.7/uws:76360
U2 - 10.1093/ibd/izab239
DO - 10.1093/ibd/izab239
M3 - Article
SN - 1078-0998
VL - 28
SP - 586
EP - 598
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 4
ER -