Dataset Information

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

ABSTRACT:

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.

SUBMITTER: Schroder AL

PROVIDER: S-EPMC9036391 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

Schroder Angie L AL Chami Belal B Liu Yuyang Y Doyle Chloe M CM El Kazzi Mary M Ahlenstiel Golo G Ahmad Gulfam G Pathma-Nathan Nimalan N Collins Geoff G Toh James J Harman Andrew A Byrne Scott S Ctercteko Grahame G Witting Paul K PK

Inflammatory bowel diseases 20220301 4

<h4>Background</h4>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.<h4>Methods</h4>Human intestinal b ...[more]

PMID: 34724042

Similar Datasets

Project description:BackgroundEmerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents of several malignant tumors and affect the tumor microenvironment and cancer evolution. Here, we investigate the prognostic value of PMNs and NETs for recurrence in patients with cervical cancer.MethodsThe study comprised 126 cervical cancer patients who were retrospectively enrolled. CD66b+ neutrophils and myeloperoxidase/citrullinated histone H3 (MPO/H3Cit)-labeled NETs were assessed by immunofluorescence, and the relationships with clinical and histopathologic features and patient outcome were evaluated.ResultsThe highest density of CD66b+ neutrophils were observed in the stromal compartment (median 55 cells/mm2). Above median densities of stromal CD66b+ neutrophils and NETs were significantly associated with short recurrence-free survival (RFS) (P = 0.041 and P = 0.006, respectively). Multivariate analysis identified high clinical stage (hazard ratio [HR] 6.40; 95% confidence interval [CI] 3.51-11.64; P < 0.001), lymph node metastases (HR 4.69; 95% CI 3.09-9.66; P = 0.006) and high density of NETs (HR 2.66; 95% CI 1.21-5.82; P = 0.015) as independent prognostic factors for short RFS, whereas a high density of CD66b+ neutrophils was not significant. Patients with a high NET density showed worse recurrence status in every stage, but the difference was only significant for stage I (P = 0.042), not stages II, III, or IV (all P > 0.05). Combining stromal NET density and the tumor, nodes, metastasis (TNM) staging system had better prognostic accuracy for cervical cancer than the TNM staging system alone at five and six years respectively (P = 0.010 and P = 0.023).ConclusionStromal NET density is an independent prognostic factor for RFS in cervical cancer. Combining NETs with the TNM staging system may further improve prognostic stratification.

Dataset Information

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

Background

Methods

Results

Conclusion

Publications

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

Similar Datasets

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