Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis

Area of Science:

• Gastroenterology
• Immunology
• Cell Biology

Background:

• Inflammatory bowel disease (IBD) is linked to abnormal neutrophil extracellular trap (NET) formation and compromised intestinal barrier function.
• The specific role of NETs in altering intestinal epithelial permeability during colitis has not been fully elucidated.

Purpose of the Study:

• To investigate the impact of NETs on intestinal epithelial permeability and barrier integrity in experimental colitis models.
• To determine if NETs contribute to the pathogenesis of intestinal inflammation.

Main Methods:

• NETs abundance was assessed in colons of mice with dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.
• Intestinal barrier integrity and epithelial cell apoptosis were analyzed.
• The effect of DNase I administration on barrier function and inflammation was evaluated.

Main Results:

• NETs were significantly increased in the colons of colitis-induced mice.
• NETs were found to impair gut permeability, promote bacterial translocation, induce epithelial cell apoptosis, and disrupt tight and adherens junctions.
• Intravenous DNase I treatment restored mucosal barrier integrity, reduced bacterial dissemination, and attenuated intestinal inflammation.

Conclusions:

• NETs play a detrimental role in gut epithelial barrier function during acute colitis.
• NETs contribute to the pathogenesis of mucosal inflammation by compromising intestinal barrier integrity.