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Mesothelial cell responses to acute appendicitis or small bowel obstruction reactive ascites: Insights into
Melissa A Hausburg1,2,3,4, Kaysie L Banton5, Christopher D Cassidy6
1Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America.
Abstract:
Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g., acute appendicitis (AA), causes formation of reactive ascitic fluid (rA) that activates peritoneum surface mesothelial cells (MCs) to form adhesions. Pathologic adhesions may arise if restoration of MC-regulated fibrinolysis and secretion of glycocalyx (GCX) are disrupted. Proteins affecting these processes may originate from peritoneal rA. This is a prospective observational IRB-approved study at three Level 1 trauma centers where rA is collected prior to surgical intervention for non-perforated AA or adhesiolysis for SBO. Samples from 48 appy and 15 SBO patients were used to treat human MCs and subjected to quantification of 85 inflammatory mediators. Results were compared between patients with surgically naïve abdomens (naïve) and patients with >1 PAS. Select rA caused MCs to form clusters of fibroblastic cells, extracellular matrix fibers (FIB), and secretion of GCX. PAS and naïve patient rA fluids were clustered into "fiber-GCX" (FIB-GCX) groups: highFIB-highGCX, highFIB-lowGCX, noFIB-highGCX, noFIB-lowGCX, and noFIB-noGCX. Between groups, 26 analytes were differentially abundant including innate immune response, wound healing, and mucosal defense proteins. Factors that contributed to the differences between groups were rA-induced highFIB and history of PAS. Overall, PAS patient rA showed a muted immune response compared to rA from naïve patients. Our data suggest that abdominal surgery may negatively impact future immune responses in the abdomen. Further, quantifying immunomodulators in peritoneal rA may lead to the development a personalized approach to post-surgical adhesion treatment and prevention.
Insights
Previous abdominal surgery may alter the immune response in reactive ascitic fluid, potentially increasing adhesion formation risk. This could inform personalized treatments for post-surgical complications.
Area of Science:
- Abdominal Surgery
- Adhesion Formation
- Immunology
Background:
- Previous abdominal surgery (PAS) is linked to increased risk of small bowel obstruction (SBO) due to adhesions.
- Appendectomy (appy) is an independent risk factor for adhesion-related complications.
- Peritoneal inflammation, like acute appendicitis (AA), can lead to adhesion formation by activating mesothelial cells (MCs) via reactive ascitic fluid (rA).
Purpose of the Study:
- To investigate how reactive ascitic fluid (rA) from patients with and without previous abdominal surgery (PAS) affects human mesothelial cells (MCs).
- To identify differences in inflammatory mediators in rA between patients with and without a history of PAS.
- To explore potential mechanisms underlying adhesion formation and altered immune responses post-abdominal surgery.
Main Methods:
- Prospective observational study collecting rA from patients undergoing surgery for non-perforated AA or adhesiolysis for SBO.
- Human MCs were treated with rA from patients with surgically naïve abdomens and those with >1 PAS.
- Quantification of 85 inflammatory mediators in rA and analysis of MC responses (fibroblast-like cell clusters, extracellular matrix fibers, glycocalyx secretion).
Main Results:
- Reactive ascitic fluid (rA) from some patients induced MCs to form clusters, extracellular matrix fibers (FIB), and secrete glycocalyx (GCX).
- rA from PAS and naïve patients clustered into distinct FIB-GCX groups, with 26 differentially abundant analytes.
- rA from PAS patients exhibited a muted immune response compared to naïve patients, with rA-induced high FIB and PAS history being key differentiating factors.
Conclusions:
- Previous abdominal surgery may negatively impact the abdominal immune response.
- Differences in rA composition correlate with surgical history and influence MC behavior.
- Quantifying peritoneal rA immunomodulators may enable personalized strategies for preventing and treating post-surgical adhesions.
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